Name: synthesis of high purity nonsymmetric dialkylphosphinic acid extractants
Uploaded: 2017-10-19T12:30:00.000+00:00
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Description: Watch this Scientific Journal Video about Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants at JoVE.com

This work was supported by the National Nature Science Foundation of China (21301104), the Fundamental Research Funds for the Central Universities (FRF-TP-16-019A3), and the State Key Laboratory of Chemical Engineering (SKL-ChE-14A04).

1. Synthesis of Mono-(2,3-dimethylbutyl)phosphinic acid 18,19
<ol>
	<li>Reaction
	<ol>
		<li>Weigh 31.80 g sodium hypophosphite hydrate, 16.00 g acetic acid, 8.42 g 2,3-dimethyl-1-butene, 0.73 g di-tert-butylnperoxide (DTBP), and 25.00 g tetrahydrofuran (THF) into a 100 mL Teflon-lined stainless steel autoclave, put a magnetic stirrer into the autoclave, and seal it.</li>
		<li>Put the autoclave in a vertical tube furnace under which is a magnetic stirringapparatus.Start the magnetic stirring apparatus and set the speed at 800 rpm.</li>
		<li>Set the heating program of the temperature controller connected to the autoclave: heat from room temperature to 120 &#176;C during 90 min, maintain at 120 &#176;C for 8 h, then cool down to room temperature naturally. Start the heating program.</li>
	</ol>
	</li>
	<li>Post-treatment
	<ol>
		<li>Transfer the products into a 250 mL one-neck round-bottom flask, wash the Teflon-lining with 50 mL THF, and add it into the same flask to ensure that all the products are transferred.</li>
		<li>Remove the THF and unreacted olefins using a rotary evaporator.</li>
		<li>Transfer the residua into a 250 mL separating funnel, wash the flask with 80 mL ethyl ether and 30 mL deionized water respectively, and add them into the same separating funnel to ensure that all the products are transferred.</li>
		<li>Add 50 mL 4% NaOH solution into the above separating funnel, shake it vigorously, and separate the aqueous phase. Extract the organic phase with 20 mL 4% NaOH solutions for three times (20 mL &#215; 3) to ensure that the aqueous phase exceeds pH 10.</li>
		<li>Combine the aqueous solutions in the above step, and transfer them into a 500 mL separating funnel.</li>
		<li>Add 90 mL of 10% H2SO4 solution and 50 mL of ethyl ether, shake vigorously, and separate the organic phase; then extract the aqueous phase with 30 mL of ethyl ether for three times (30 mL &#215; 3).</li>
		<li>Combine the ethyl ether solutions in step 1.2.6, and transfer them into another 500 mL separating funnel.</li>
		<li>Wash it with 100 mL of saturated NaCl solutions four times (100 mL &#215; 4).</li>
		<li>Add 4 g of anhydrous MgSO4 to remove any soluble water. Filter to remove the solid, and collect the liquid in a clean 250 mL one-neck round-bottom flask.</li>
		<li>Remove the ethyl ether using the rotary evaporator to obtain 17.92 g of the crude product.</li>
	</ol>
	</li>
</ol>
2. Purification of Mono-(2,3-dimethylbutyl)phosphinic Acid
<ol>
	<li>Preparation of amantadine solution
	<ol>
		<li>Dissolve 22.28 g of amantadine hydrochloride in 100 mL of deionized water in a 500 mL beaker.</li>
		<li>Add 100 mL of saturated NaOH solution, and stir for 5 min.</li>
		<li>Add 150 mL of ethyl ether, and stir until the white precipitate generated in step 2.1.2 disappears.</li>
		<li>Transfer the solutions into a 500 mL separating funnel, wash the beaker with ethyl ether for three times (50 mL &#215; 3), and combine them into the same separating funnel.</li>
		<li>Separate the aqueous phase, and wash the organic phase with saturated NaCl solutions five times (100 mL &#215; 5).</li>
		<li>Add 4 g of anhydrous MgSO4 to remove any soluble water. Filter to obtain the amantadine ethyl ether solution.</li>
	</ol>
	</li>
	<li>Preparation of amantadine &#8729; mono-(2,3-dimethylbutyl)phosphinic acid salt
	<ol>
		<li>Add drop-wise the crude mono-(2,3-dimethylbutyl)phosphinic acid product to the amantadine solution. During dropping add 150 mL of ethyl ether to ensure that it can stir properly.</li>
		<li>Wash the one-neck round-bottom flask containing the mono-(2,3-dimethylbutyl)phosphinic acid product with 50 mL of ethyl ether to ensure that all the product is transferred to the amantadine solution. Stir for 30 min, and let it sit overnight.</li>
		<li>Filter under reduced pressure, and wash the filter cake with 200 mL ethyl ether.</li>
	</ol>
	</li>
	<li>Release the mono-(2,3-dimethylbutyl)phosphinic acid
	<ol>
		<li>Transfer the filtered cake into a 500 mL beaker, add 80 mL of 1 M HCl, and stir for 5 min.</li>
		<li>Add 70 mL ethyl acetate, and stir for another 5 min.</li>
		<li>Transfer the solutions into a 250 mL separating funnel and separate the aqueous phase.</li>
		<li>Extract the aqueous phase with 40 mL ethyl acetate again and combine the ethyl acetate solutions.</li>
		<li>Wash the ethyl acetate solution with 30 mL of 1 M HCl twice (30 mL &#215; 2) and saturated NaCl three times (80 mL &#215; 3), sequentially.</li>
		<li>Add 4 g anhydrous MgSO4 to remove any soluble water. Filter and collect the liquid in a 250 mL one-neck round-bottom flask.</li>
		<li>Remove the ethyl acetate using the rotary evaporator, and obtain 12.45 g of the pure mono-(2,3-dimethylbutyl)phosphinic acid (Yield: 82.9%).</li>
	</ol>
	</li>
</ol>
3. Synthesis of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic Acid
<ol>
	<li>Reaction
	<ol>
		<li>Transfer all of the pure mono-(2,3-dimethylbutyl)phosphinic acid product into a 100 mL Teflon-lined stainless steel autoclave, add 4.95 g of acetic acid, 25.39 g of diisobutylene, 0.30 g of DTBP, put a magnetic stirrer into the autoclave, and seal it.</li>
		<li>Put the autoclave in a vertical tube furnace under which is a magnetic stirring apparatus, and start the magnetic stirring apparatus.</li>
		<li>Set the heating program of the temperature controller: heat from room temperature to 135 &#176;C during 90 min, maintain at 135 &#176;C for 8 h, then cool down to room temperature naturally. Start the heating program.</li>
		<li>When the reaction system cools down to room temperature, add another 0.30 g of DTBP, and restart the heating program.</li>
		<li>Repeat step 3.1.4 once.</li>
	</ol>
	</li>
	<li>Post-treatment
	<ol>
		<li>Dilute the product with 100 mL ethyl ether, and then transfer to a 250 mL separating funnel.</li>
		<li>Wash it with 30 mL of 4% NaOH three times (30 mL &#215; 3) to ensure that aqueous phase exceeds pH 10.</li>
		<li>Add 70 mL of 10% H2SO4 solution to acidify the product.</li>
		<li>Wash it with saturated NaCl solution several times (80 mL each) until the aqueous phase pH equals pH 6-7.</li>
		<li>Add 4 g of anhydrous MgSO4 to remove any soluble water. Filter to remove the solid, and collect the liquid in a clean 250 mL one-neck round-bottom flask.</li>
		<li>Remove the ethyl ether and unreacted olefins using the rotary evaporator to obtain 15.10 g of crude product.</li>
	</ol>
	</li>
</ol>
4. Purification of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic Acid
<ol>
	<li>Obtain pure co-(2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid complex
	<ol>
		<li>Dissolve 2.30 g of NaOH in 40 mL deionized water. Add the NaOH solution to the flask containing the crude (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid product, and shake it vigorously for 5 min.</li>
		<li>Add 0.5 M CoCl2 solution dropwise while shaking until no more blue precipitate is generated and the solution in the flask is pink.</li>
		<li>Filter and wash the blue precipitate with deionized water until the filter cake is colorless.</li>
		<li>Transfer the filter cake into a 250 mL beaker, add 100 mL of acetone, seal it with preservative film, and then refrigerate it at 4 &#176;C for one night.</li>
		<li>Pulverize the blue precipitate to release any impurities trapped in the bulk.</li>
		<li>Filter and wash it with 100 mL of fresh acetone. Dry the filter cake at room temperature, and then transfer it into a 250 mL separating funnel.</li>
	</ol>
	</li>
	<li>Regenerate the (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid
	<ol>
		<li>Add 120 mL ethyl ether and 80 mL 10% H2SO4, and shake vigorously until the blue precipitate disappears.</li>
		<li>Separate the aqueous phase,wash the organic phase sequentially with 30 mL of 10% H2SO4 once and saturated NaCl solutions several times (80 mL each) until the aqueous phase pH equals pH 6-7.</li>
		<li>Add 4 g of anhydrous MgSO4 to remove any soluble water. Filter to remove the solid and collect the liquid in a clean 250 mL one-neck round-bottom flask.</li>
		<li>Remove the ethyl ether using the rotary evaporator, and obtain 11.46 g of the pure product (Yield: 52.8%).</li>
	</ol>
	</li>
</ol>

<ol>
	<li>Swain, B., Otu, E. O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Competitive+extraction+of+lanthanides+by+solvent+extraction+using+Cyanex+272:+Analysis,+classification+and+mechanism.">Competitive extraction of lanthanides by solvent extraction using Cyanex 272: Analysis, classification and mechanism.</a> Sep Purif Technol. 83, 82-90 (2011).</li><li>Wang, Y. 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=The+novel+extraction+process+based+on+CYANEX+(R)+572+for+separating+heavy+rare+earths+from+ion-adsorbed+deposit.">The novel extraction process based on CYANEX (R) 572 for separating heavy rare earths from ion-adsorbed deposit.</a> Sep Purif Technol. 151, 303-308 (2015).</li><li>Regel-Rosocka, M., Staszak, K., Wieszczycka, K., Masalska, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Removal+of+cobalt(II)+and+zinc(II)+from+sulphate+solutions+by+means+of+extraction+with+sodium+bis(2,4,4-trimethylpentyl)phosphinate+(Na-Cyanex+272).">Removal of cobalt(II) and zinc(II) from sulphate solutions by means of extraction with sodium bis(2,4,4-trimethylpentyl)phosphinate (Na-Cyanex 272).</a> Clean Technol Envir. 18 (6), 1961-1970 (2016).</li><li>Hereijgers, J., 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=Separation+of+Co(II)/Ni(II)+with+Cyanex+272+using+a+flat+membrane+microcontactor:+Stripping+kinetics+study,+upscaling+and+continuous+operation.">Separation of Co(II)/Ni(II) with Cyanex 272 using a flat membrane microcontactor: Stripping kinetics study, upscaling and continuous operation.</a> Chem Eng Res Des. 111, 305-315 (2016).</li><li>Lee, M. S., Banda, R., Min, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Separation+of+Hf(IV)-Zr(IV)+in+H2SO4+solutions+using+solvent+extraction+with+D2EHPA+or+Cyanex+272+at+different+reagent+and+metal+ion+concentrations.">Separation of Hf(IV)-Zr(IV) in H2SO4 solutions using solvent extraction with D2EHPA or Cyanex 272 at different reagent and metal ion concentrations.</a> Hydrometallurgy. 152, 84-90 (2015).</li><li>Noori, M., Rashchi, F., Babakhani, A., Vahidi, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Selective+recovery+and+separation+of+nickel+and+vanadium+in+sulfate+media+using+mixtures+of+D2EHPA+and+Cyanex+272.">Selective recovery and separation of nickel and vanadium in sulfate media using mixtures of D2EHPA and Cyanex 272.</a> Sep Purif Technol. 136, 265-273 (2014).</li><li>Li, X. B., 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=Thermodynamics+and+mechanism+of+vanadium(IV)+extraction+from+sulphate+medium+with+D2EHPA,+EHEHPA+and+CYANEX+272+in+kerosene.">Thermodynamics and mechanism of vanadium(IV) extraction from sulphate medium with D2EHPA, EHEHPA and CYANEX 272 in kerosene.</a> Trans Nonferrous Met Soc China. 22 (2), 461-466 (2012).</li><li>Das, D., 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=Effect+of+the+nature+of+organophosphorous+acid+moiety+on+co-extraction+of+U(VI)+and+mineral+acid+from+aqueous+solutions+using+D2EHPA,+PC88A+and+Cyanex+272.">Effect of the nature of organophosphorous acid moiety on co-extraction of U(VI) and mineral acid from aqueous solutions using D2EHPA, PC88A and Cyanex 272.</a> Hydrometallurgy. 152, 129-138 (2015).</li><li>Baba, A. A., 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=Extraction+of+copper+from+leach+liquor+of+metallic+component+in+discarded+cell+phone+by+Cyanex+(R)+272.">Extraction of copper from leach liquor of metallic component in discarded cell phone by Cyanex (R) 272.</a> JESTEC. 11 (6), 861-871 (2016).</li><li>Du, R. B., 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=Microwave-assisted+synthesis+of+dialkylphosphinic+acids+and+a+structure-reactivity+study+in+rare+earth+metal+extraction.">Microwave-assisted synthesis of dialkylphosphinic acids and a structure-reactivity study in rare earth metal extraction.</a> RSC Adv. 5 (126), 104258-104262 (2015).</li><li>Du, R. B., 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=alpha,+beta-Substituent+effect+of+dialkylphosphinic+acids+on+anthanide+extraction.">alpha, beta-Substituent effect of dialkylphosphinic acids on anthanide extraction.</a> RSC Adv. 6 (61), 56004-56008 (2016).</li><li>Wang, J. L., Xu, S. X., Li, L. Y., Li, J. <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+organic+phosphinic+acids+and+studies+on+the+relationship+between+their+structure+and+extraction-separation+performance+of+heavy+rare+earths+from+HNO3+solutions.">Synthesis of organic phosphinic acids and studies on the relationship between their structure and extraction-separation performance of heavy rare earths from HNO3 solutions.</a> Hydrometallurgy. 137, 108-114 (2013).</li><li>Hino, A., Nishihama, S., Hirai, T., Komasawa, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Practical+study+of+liquid-liquid+extraction+process+for+separation+of+rare+earth+elements+with+bis+(2-ethylhexyl)+phosphinic+acid.">Practical study of liquid-liquid extraction process for separation of rare earth elements with bis (2-ethylhexyl) phosphinic acid.</a> J Chem Eng Jpn. 30 (6), 1040-1046 (1997).</li><li>Ju, Z. J., 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=Synthesis+and+extraction+performance+of+di-decylphosphinic+acid.">Synthesis and extraction performance of di-decylphosphinic acid.</a> Chin J Nonferrous Met. 20 (11), 2254-2259 (2010).</li><li>Li, L. Y., 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=Dialkyl+phosphinic+acids:+Synthesis+and+applications+as+extractant+for+nickel+and+cobalt+separation.">Dialkyl phosphinic acids: Synthesis and applications as extractant for nickel and cobalt separation.</a> Trans Nonferrous Met Soc China. 20, 205-210 (2010).</li><li>Wang, J. 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=Solvent+extraction+of+rare+earth+ions+from+nitrate+media+with+new+extractant+di-(2,3-dimethylbutyl)-phosphinic+acid.">Solvent extraction of rare earth ions from nitrate media with new extractant di-(2,3-dimethylbutyl)-phosphinic acid.</a> J Rare Earths. 34 (7), 724-730 (2016).</li><li>Hu, W. X. <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+properties+of+di-tertiary+alkylphosphinic+acids.">Synthesis and properties of di-tertiary alkylphosphinic acids.</a> Chem J Chin Univ-Chin. 15 (6), 849-853 (1994).</li><li>Wang, J. L., Chen, G., Xu, S. M., Li, L. Y. <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+novel+nonsymmetric+dialkylphosphinic+acid+extractants+and+studies+on+their+extraction-separation+performance+for+heavy+rare+earths.">Synthesis of novel nonsymmetric dialkylphosphinic acid extractants and studies on their extraction-separation performance for heavy rare earths.</a> Hydrometallurgy. 154, 129-136 (2015).</li><li>Wang, J. L., Xie, M. Y., Wang, H. J., Xu, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Solvent+extraction+and+separation+of+heavy+rare+earths+from+chloride+media+using+nonsymmetric+(2,3-dimethylbutyl)(2,4,4'-trimethylpentyl)phosphinic+acid.">Solvent extraction and separation of heavy rare earths from chloride media using nonsymmetric (2,3-dimethylbutyl)(2,4,4'-trimethylpentyl)phosphinic acid.</a> Hydrometallurgy. 167, 39-47 (2017).</li><li>Menoyo, B., Elizalde, M. P., Almela, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+the+degradation+compounds+formed+by+the+oxidation+of+thiophosphinic+acids+and+phosphine+sulfides+with+nitric+acid.">Determination of the degradation compounds formed by the oxidation of thiophosphinic acids and phosphine sulfides with nitric acid.</a> Anal Sci. 18 (7), 799-804 (2002).</li><li>Darvishi, D., 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=Synergistic+effect+of+Cyanex+272+and+Cyanex+302+on+separation+of+cobalt+and+nickel+by+D2EHPA.">Synergistic effect of Cyanex 272 and Cyanex 302 on separation of cobalt and nickel by D2EHPA.</a> Hydrometallurgy. 77, 227-238 (2005).</li></ol>

The authors have nothing to disclose.

The most critical step within the protocol is the mono-alkylphosphinic acid synthesis (Figure 1a). In this reaction, a higher yield and less dialkylphosphinic acid by-product is better. Increasing the molar ratio of NaH2PO2/olefin A will improve the yield and inhibit the generation of dialkylphosphinic acid by-product. However, a large NaH2PO2 dosage will also increase the cost and cause a stirring problem. The preferred molar ratio of NaH2PO2/olefin A is 3:1. As a solvent, THF is better than n-octane, 1,4-dioxane, and cyclohexane in this reaction. As to the initiator, DTBP is better than 2,2-azobisisobutyronitrile (AIBN)18. To separate the mono-alkylphosphinic acid from the di-alkylphosphinic acid by-product, the amantadine method can be adopted. The mono-alkylphosphinic acid can react with amantadine to generate a white precipitation, while the di-alkylphosphinic acid cannot due to its large spatial restrictions and it still remains in the organic solution. Separate the white precipitation by filtration, and add an inorganic strong acid (like HCl or H2SO4) to regenerate the mono-alkylphosphinic acid, so that complete separation of the mono-alkylphosphinic acid and di-alkylphosphinic acid by-product can be realized.
In the NSDAPA synthesis (Figure 1b), the molar ratio of olefin B/mono-alkylphosphinic acid is more than 1:1 (2:1-4:1 is preferred) and the excess olefin B plays the role of the solvent. Though the olefin B is in excess, the mono-alkylphosphinic acid cannot react completely. The unreacted mono-alkylphosphinic acid will enter into the aqueous phase from the organic phase when it reacts with a base (like NaOH or KOH), so it can be easily removed simply by the base-acid post-treatment. During the base-acid post-treatment, the NSDAPA always remains in the organic phase, and thus its crude product always contains organic impurities such as unreacted olefin B, free radical fragments, oligomers, etc. These organic impurities are soluble in acetone, while the solubility of Co-NSDAPA complex is very small in icy acetone. This difference offers a way to further purify NSDAPA: react the NSDAPA with Co2+ to form a Co-NSDAPA complex, wash the complex with icy acetone to remove the organic impurities, and then add strong acid (like H2SO4 or HCl) to the complex to regenerate the NSDAPA.
This protocol describes a universal method for NSDAPA synthesis and purification. Compared with the traditional NSDAPA synthetic method with PH3 as the phosphorus source, our method has the advantages of low toxicity, mild reaction conditions, easy purification, and potential for large-scale production. This method offers a way to finely adjust the performance of dialkylphosphinic acids. Like other organophosphorus acid extractants such as P204, P507, and Cyanex 272, NSDAPA can also be used in hydrometallurgy filed for extraction and separation of rare earth ions, non-ferrous metals, rare metals, actinides, etc. Our synthetic method of NSDAPA makes it possible to explore a number of potential separation systems with this class of extractants.

Acidic organophosphorus extractants are widely used in the traditional hydrometallurgy field for extraction and separation of rare earth ions1,2, non-ferrous metals (like Co/Ni3,4), rare metals (such as Hf/Zr5, V6,7), actinides8, etc. In recent years, they have also attracted more attention in the fields of secondary resource recycling and high-level liquid waste disposal9. Di-(2-ethylhexyl)phosphoric acid (D2EHPA or P204), 2-ethylhexylphosphoric acid mono-2-ethylhexyl ester (EHEHPA, PC 88A, or P507), and Di-(2,4,4&#39;-trimethylpentyl)-phosphinic acid (Cyanex272), which are representatives of dialkylphosphoric acids, alkylphosphoric acid mono-alkyl esters, and dialkylphosphinic acids respectively, are the most commonly used extractants. Their acidity decreases in the following sequence: P204 &#62; P507 &#62; Cyanex 272. The corresponding extraction ability, extraction capacity, and stripping acidity are all in the order of P204 &#62; P507 &#62; Cyanex 272, and the separation performance is in the opposite order. These three extractants are effective in most cases. However, there are still some conditions where they are not so efficient: in heavy rare earths separation, of which the existing main problems are the poor selectivity and high stripping acidity for P204 and P507, low extraction capacity, and emulsion tendency during extraction for Cyanex 272. Thus, the development of novel extractants has drawn greater attention in recent years.
The class of dialkylphosphinic acid extractants is considered to be one of the most important research aspects to develop new extractants. Recent research showed that the extraction ability of dialkylphosphinic acids depends largely on the structure of the alkyl substituent10,11. It can be a wide range from significantly higher than that of P507 to lower than that of Cyanex 27212. However, the exploration of novel dialkylphosphinic acid extractants is restricted to the commercial olefin structure10,12,13,14,15,16. Though dialkylphosphinic acid extractants can also be synthesized by the Grignard-reaction method, the reaction conditions are rigorous12,17.
NSDAPA, of which the two alkyls are different, opens a door to the exploration of new extractants. It makes the structures of dialkylphosphinic acid more diverse, and its extraction and separation performance can be fine-tuned by modifying both of its alkyl structures. The traditional synthetic method of NSDAPA used PH3 as a phosphorus source, which has many drawbacks like high toxicity, rigorous reaction conditions, and difficult purification. Recently we reported a new method to synthesize NSDAPA using sodium hypophosphite as a phosphorus source (see Figure 1) and successfully synthesized three NSDAPAs18. This detailed protocol can help new practitioners repeat the experiments and master the synthetic method of NSDAPA extractants. We take (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid as an example. The names and structures of olefin A, the mono-alkylphosphinic acid intermediate, olefin B, and the corresponding NSDAPA are shown in Table 1.

<table><tbody><tr><td>2,3-dimethyl-1-butene</td><td>Adamas Reagent Co., Ltd.</td><td></td><td>Molecular formula: C&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;6&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;H&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;12&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;, purity &amp;ge;99%&lt;/span&gt;</td></tr><tr><td>diisobutylene</td><td>Shanghai&amp;nbsp;Aladdin&amp;nbsp;Bio-Chem&amp;nbsp;Technology&amp;nbsp;Co.,&amp;nbsp;LTD</td><td></td><td>Molecular formula: C&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;8&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;H&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;16&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;, purity 97%&lt;/span&gt;</td></tr><tr><td>acetic acid</td><td>Sinopharm Chemical Reagent Co., Ltd.</td><td></td><td>Molecular formula: C&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;2&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;H&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;4&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;O&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;2&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;, purity &amp;ge;99.5%&lt;/span&gt;</td></tr><tr><td>di-&lt;span class=&quot;font9&quot;&gt;tert&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;-butylnperoxide&lt;/span&gt;</td><td>Sinopharm Chemical Reagent Co., Ltd.</td><td></td><td>Molecular formula: C&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;8&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;H&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;18&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;O&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;2&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;, purity &amp;ge;97.0%&lt;/span&gt;</td></tr><tr><td>tetrahydrofuran</td><td>Beijing Chemical Works</td><td></td><td>Molecular formula: C&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;4&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;H&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;8&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;O, purity A.R.&lt;/span&gt;</td></tr><tr><td>ethyl ether</td><td>Sinopharm Chemical Reagent Co., Ltd.</td><td></td><td>Molecular formula: C&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;4&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;H&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;10&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;O, purity &amp;ge;99.7%&lt;/span&gt;</td></tr><tr><td>ethyl acetate</td><td>Xilong Chemical Co., Ltd.</td><td></td><td>Molecular formula: C&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;4&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;H&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;8&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;O&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;2&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;, purity &amp;ge;99.5%&lt;/span&gt;</td></tr><tr><td>acetone</td><td>Beijing Chemical Works</td><td></td><td>Molecular formula: C&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;3&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;H&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;6&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;O, purity &amp;ge;99.5%&lt;/span&gt;</td></tr><tr><td>sodium hydroxide</td><td>Xilong Chemical Co., Ltd.</td><td></td><td>Molecular formula: NaOH, purity &amp;ge;96.0%</td></tr><tr><td>concentrated sulfuric acid</td><td>Sinopharm Chemical Reagent Co., Ltd.</td><td></td><td>Molecular formula: H&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;2&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;SO&lt;/span&gt;&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;4&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;, purity 95-98%&lt;/span&gt;</td></tr><tr><td>hydrochloric acid</td><td>Beijing Chemical Works</td><td></td><td>Molecular formula: HCl, purity 36-38%</td></tr><tr><td>sodium chloride</td><td>Sinopharm Chemical Reagent Co., Ltd.</td><td></td><td>Molecular formula: NaCl, purity &amp;ge;99.5%</td></tr><tr><td>anhydrous magnesium sulfate</td><td>Tianjin Jinke Institute of Fine Chemical Industry</td><td></td><td>Molecular formula: MgSO&lt;span class=&quot;font8&quot;&gt;&lt;sub&gt;4&lt;/sub&gt;&lt;/span&gt;&lt;span class=&quot;font7&quot;&gt;, purity &amp;ge;99.0%&lt;/span&gt;</td></tr></tbody></table>

synthesis of high purity nonsymmetric dialkylphosphinic acid extractants

We present the synthesis of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid as an example to demonstrate a method for the synthesis of high purity nonsymmetric dialkylphosphinic acid extractants. Low toxic sodium hypophosphite was chosen as the phosphorus source to react with olefin A (2,3-dimethyl-1-butene) to generate a monoalkylphosphinic acid intermediate. Amantadine was adopted to remove the dialkylphosphinic acid byproduct, as only the monoalkylphosphinic acid can react with amantadine to form an amantadine&#8729;mono-alkylphosphinic acid salt, while the dialkylphosphinic acid cannot react with amantadine due to its large steric hindrance. The purified monoalkylphosphinic acid was then reacted with olefin B (diisobutylene) to yield nonsymmetric dialkylphosphinic acid (NSDAPA). The unreacted monoalkylphosphinic acid can be easily removed by a simple base-acid post-treatment and other organic impurities can be separated out through the precipitation of the cobalt salt. The structure of the (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid was confirmed by 31P NMR, 1H NMR, ESI-MS, and FT-IR. The purity was determined by a potentiometric titration method, and the results indicate that the purity can exceed 96%.

31P NMR spectra were collected for the mono-(2,3-dimethylbutyl)phosphinic acid before and after purification by the amantadine method (Figure 1a-b). 31P NMR spectra, 1H NMR spectra, MS spectra, and FT-IR spectra were collected for (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid (see Figure 3, Figure 4, Figure 5, and Figure 6, respectively) after purification by a cobalt salt precipitation method. Potentiometric titration curves of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid were recorded (Figure 7)19.
During the mono-alkylphosphinic acid synthesis, it is difficult to avoid the generation of corresponding dialkylphosphinic acid byproduct (see Figure 1a), which cannot be removed by the base-acid post-treatment. That is the reason for the absorption peak (62.507 ppm) of di-(2,3-dimethylbutyl)phosphinic acid in Figure 2a. When olefin A was 1-octene or cyclohexene, similar phenomena occurred18. 2,4-dimethyl-1-heptene, which contains nine carbon atoms, was also tested but the same phenomena also occurred. Figure 2b shows the 31P NMR spectra of pure mono-(2,3-dimethylbutyl)phosphinic acid.
Structural characterization of the (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid: 
31P NMR (243 MHz, CDCl3) &#948; (Figure 3): 61.40(s). 1H NMR (600 MHz, CDCl3) &#948; (Figure 4): 0.82-0.88 (m, 6H, 2CH3), 0.92 (s, 9H, 3CH3), 1.01-1.04 (m, 3H, CH3), 1.12-1.15 (m, 3H, CH3), 1.15-1.21 (m, 1H), 1.32-1.38 (m, 1H), 1.41-1.49 (m, 1H), 1.51-1.60 (m, 1H), 1.61-1.78 (m, 3H), 1.87-1.95 (m, 1H), 2.04-.14 (m, 1H), 11.862 (s, 1H, OH).
ESI-MS (+) m/z (Figure 5a): 263 [M+H]+, 304 [M+C3H6]+, 525 [2M+H]+, 547 [2M+Na]+, 567 [2M+C3H7]+. ESI-MS (-) m/z (Figure 5b): 261 [M-H]-, 523 [2M-H]-, 566 [2M+C3H7-H]-. FT-IR wavenumbers (cm-1) (Figure 6): 2876.55-2902.84 C-H stretching, 2619.51 O-H stretching caused by dimer formation, 1667.29 O-H bending, 1467.91 C-H bending, 1366.13 C-H rocking, 1237.41 C-C stretching of the tert-butyl group, 1165.57 P=O stretching, 962.69 P-O(H) stretching, 821.97 P-C stretching. The relevant vibrational characteristic bands are similar to those of phosphonic acids, phosphoric acids, and other phosphinic acids20,21.
The 31P and 1H NMR spectra, ESI-MS spectra, and FT-IR spectrum confirmed the structure of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid. The potentiometric titration results (Figure 719) indicate that the purity of the final product can exceed 96%.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56156/56156fig1.jpg" /> 
Figure 1. Synthesis route of NSDAPA acids. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56156/56156fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/56156/56156fig2.jpg" /> 
Figure 2.31P NMR spectra (243 MHz, CDCl3) of mono-(2,3-dimethylbutyl)phosphinic acid (a) before and (b) after purification by the amantadine method. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56156/56156fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56156/56156fig3.jpg" /> 
Figure 3.31P NMR spectrum (243 MHz, CDCl3) of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid after purification by the cobalt salt precipitation method. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56156/56156fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/56156/56156fig4.jpg" /> 
Figure 4. 1H NMR spectrum (600 MHz, CDCl3) of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid after purification by the cobalt salt precipitation method. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56156/56156fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/56156/56156fig5.jpg" /> 
Figure 5. ESI-MS spectra of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid after purification by cobalt salt precipitation method, (a) Positive and (b) Negative. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56156/56156fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/56156/56156fig6.jpg" /> 
Figure 6. FT-IR spectrum of pure (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid after purification by the cobalt salt precipitation method. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56156/56156fig6large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 7" class="xfigimg" src="/files/ftp_upload/56156/56156fig7.jpg" /> 
Figure 7. Potentiometric titration curve of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid (m = 0.1270 g) in 75% alcohol (v/v) with 0.1127 mol/L NaOH.&#160;<a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56156/56156fig7large.jpg" style="font-size: 14px;" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants at JoVE.com

Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants

A protocol for the synthesis of high purity nonsymmetric dialkylphosphinic acid extractants is presented, taking (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid as an example.

We present the synthesis of (2,3-dimethylbutyl)(2,4,4&#39;-trimethylpentyl)phosphinic acid as an example to demonstrate a method for the synthesis of high ...

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Acid-base and Solubility Equilibria

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7.4K Views.  University of Science and Technology Beijing. Een protocol voor de synthese van hoge zuiverheid nonsymmetric dialkylphosphinic zure extractants wordt gepresenteerd, nemen (2,3-dimethylbutyl) (2,4, 4'-trimethylpentyl) phosphinic zuur als voorbeeld.

Video: Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants

Compact Quantum Dots for Single-molecule Imaging

Single-molecule imaging is an important tool for understanding the mechanisms of biomolecular function and for visualizing the spatial and temporal heterogeneity of molecular behaviors that underlie cellular biology 1-4. To image an individual molecule of interest, it is typically conjugated to a fluorescent tag (dye, protein, bead, or quantum dot) and observed with epifluorescence or total internal reflection fluorescence (TIRF) microscopy. While dyes and fluorescent proteins have been the mainstay of fluorescence imaging for decades, their fluorescence is unstable under high photon fluxes necessary to observe individual molecules, yielding only a few seconds of observation before complete loss of signal. Latex beads and dye-labeled beads provide improved signal stability but at the expense of drastically larger hydrodynamic size, which can deleteriously alter the diffusion and behavior of the molecule under study.
Quantum dots (QDs) offer a balance between these two problematic regimes. These nanoparticles are composed of semiconductor materials and can be engineered with a hydrodynamically compact size with exceptional resistance to photodegradation 5. Thus in recent years QDs have been instrumental in enabling long-term observation of complex macromolecular behavior on the single molecule level. However these particles have still been found to exhibit impaired diffusion in crowded molecular environments such as the cellular cytoplasm and the neuronal synaptic cleft, where their sizes are still too large 4,6,7.
Recently we have engineered the cores and surface coatings of QDs for minimized hydrodynamic size, while balancing offsets to colloidal stability, photostability, brightness, and nonspecific binding that have hindered the utility of compact QDs in the past 8,9. The goal of this article is to demonstrate the synthesis, modification, and characterization of these optimized nanocrystals, composed of an alloyed HgxCd1-xSe core coated with an insulating CdyZn1-yS shell, further coated with a multidentate polymer ligand modified with short polyethylene glycol (PEG) chains (Figure 1). Compared with conventional CdSe nanocrystals, HgxCd1-xSe alloys offer greater quantum yields of fluorescence, fluorescence at red and near-infrared wavelengths for enhanced signal-to-noise in cells, and excitation at non-cytotoxic visible wavelengths. Multidentate polymer coatings bind to the nanocrystal surface in a closed and flat conformation to minimize hydrodynamic size, and PEG neutralizes the surface charge to minimize nonspecific binding to cells and biomolecules. The end result is a brightly fluorescent nanocrystal with emission between 550-800 nm and a total hydrodynamic size near 12 nm. This is in the same size range as many soluble globular proteins in cells, and substantially smaller than conventional PEGylated QDs (25-35 nm).

We describe the preparation of colloidal quantum dots with minimized hydrodynamic size for single-molecule fluorescence imaging. Compared to conventional quantum dots, these nanoparticles are similar in size to globular proteins and are optimized for single-molecule brightness, stability against photodegradation, and resistance to nonspecific binding to proteins and cells.

Single-molecule imaging is an important tool for  understanding the mechanisms of biomolecular function and for visualizing the  spatial and temporal ...

Engineering

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.

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

Preparation of Highly Porous Coordination Polymer Coatings on Macroporous Polymer Monoliths for Enhanced Enrichment of Phosphopeptides

We describe a protocol for the preparation of hybrid materials based on highly porous coordination polymer coatings on the internal surface of macroporous polymer monoliths. The developed approach is based on the preparation of a macroporous polymer containing carboxylic acid functional groups and the subsequent step-by-step solution-based controlled growth of a layer of a porous coordination polymer on the surface of the pores of the polymer monolith. The prepared metal-organic polymer hybrid has a high specific micropore surface area. The amount of iron(III) sites is enhanced through metal-organic coordination on the surface of the pores of the functional polymer support. The increase of metal sites is related to the number of iterations of the coating process.
The developed preparation scheme is easily adapted to a capillary column format. The functional porous polymer is prepared as a self-contained single-block porous monolith within the capillary, yielding a flow-through separation device with excellent flow permeability and modest back-pressure. The metal-organic polymer hybrid column showed excellent performance for the enrichment of phosphopeptides from digested proteins and their subsequent detection using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The presented experimental protocol is highly versatile, and can be easily implemented to different organic polymer supports and coatings with a plethora of porous coordination polymers and metal-organic frameworks for multiple purification and/or separation applications.

A procedure for the preparation of porous hybrid separation media composed of a macroporous polymer monolith internally coated by a high surface area microporous coordination polymer is presented.

We describe a protocol for the preparation of hybrid materials based on highly porous coordination polymer coatings on the internal surface of macroporous ...

Extraction and Characterization of Surfactants from Atmospheric Aerosols

Surface-active compounds, or surfactants, present in atmospheric aerosols are expected to play important roles in the formation of liquid water clouds in the Earth&#39;s atmosphere, a central process in meteorology, hydrology, and for the climate system. But because specific extraction and characterization of these compounds have been lacking for decades, very little is known on their identity, properties, mode of action and origins, thus preventing the full understanding of cloud formation and its potential links with the Earth&#39;s ecosystems.
In this paper we present recently developed methods for 1) the targeted extraction of all the surfactants from atmospheric aerosol samples and for the determination of 2) their absolute concentrations in the aerosol phase and 3) their static surface tension curves in water, including their Critical Micelle Concentration (CMC). These methods have been validated with 9 references surfactants, including anionic, cationic and non-ionic ones. Examples of results are presented for surfactants found in fine aerosol particles (diameter &#60;1 &#956;m) collected at a coastal site in Croatia and suggestions for future improvements and other characterizations than those presented are discussed.

Methods are presented for the targeted extraction of surfactants present in atmospheric aerosols and the determination of their absolute concentrations and surface tension curves in water, including their Critical Micelle Concentration (CMC).

Surface-active compounds, or surfactants, present in atmospheric aerosols are expected to play important roles in the formation of liquid water clouds in ...

Environment

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles (PPAs) and Related Biomaterials

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). Traditional PAs possess charged amino acids as solubilizing groups (lysine, arginine), which are directly connected to a lipid segment or can contain a linker region made of neutral amino acids. Tuning the peptide sequence of PAs can yield diverse morphologies. Similarly, PPAs possess a hydrophobic segment and neutral amino acids, but also contain polyamine molecules as water solubilizing (hydrophilic) groups. As is the case with PAs, PPAs can also self-assemble into diverse morphologies, including small rods, twisted nano-ribbons, and fused nano-sheets, when dissolved in water. However, the presence of both primary and secondary amines on a single polyamine molecule poses a significant challenge when synthesizing PPAs. In this paper, we show a simple protocol, based on literature precedents, to achieve a facile synthesis of PPAs using solid phase peptide synthesis (SPPS). This protocol can be extended to the synthesis of PAs and other similar systems. We also illustrate the steps that are needed for cleavage from the resin, identification, and purification.

Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles PPAs and Related Biomaterials

The synthesis of polyamine-based peptide amphiphiles (PPAs) is a significant challenge due to the presence of multiple amine nitrogens, which requires judicious use of protecting groups to mask these reactive functionalities. In this paper, we describe a facile method for the preparation of these new class of self-assembling molecules.

Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). ...

Synthesis of Esters Via a Greener Steglich Esterification in Acetonitrile

The Steglich esterification is a widely-used reaction for the synthesis of esters from carboxylic acids and alcohols. While efficient and mild, the reaction is commonly performed using chlorinated or amide solvent systems, which are hazardous to human health and the environment. Our methodology utilizes acetonitrile as a greener and less hazardous solvent system. This protocol exhibits rates and yields that are comparable to traditional solvent systems and employs an extraction and wash sequence that eliminates the need for the purification of the ester product via column chromatography. This general method can be used to couple a variety of carboxylic acids with 1&#176; and 2&#176; aliphatic alcohols, benzylic and allylic alcohols, and phenols to obtain pure esters in high yields. The goal of the protocol detailed here is to provide a greener alternative to a common esterification reaction, which could serve useful for ester synthesis in both academic and industrial applications.

A modified Steglich esterification reaction was used to synthesize a small library of ester derivatives with primary and secondary alcohols. The methodology uses a non-halogenated and greener solvent, acetonitrile, and enables product isolation in high yields without the need for chromatographic purification.

The Steglich esterification is a widely-used reaction for the synthesis of esters from carboxylic acids and alcohols. While efficient and mild, the ...

Preparation of Poly(pentafluorophenyl acrylate) Functionalized SiO2 Beads for Protein Purification

We demonstrate a simple method to prepare poly(pentafluorophenyl acrylate) (poly(PFPA)) grafted silica beads for antibody immobilization and subsequent immunoprecipitation (IP) application. The poly(PFPA) grafted surface is prepared via a simple two-step process. In the first step, 3-aminopropyltrimethoxysilane (APTMS) is deposited as a linker molecule onto the silica surface. In the second step, poly(PFPA) homopolymer, synthesized via the reversible addition and fragmentation chain transfer (RAFT) polymerization, is grafted to the linker molecule through the exchange reaction between the pentafluorophenyl (PFP) units on the polymer and the amine groups on APTMS. The deposition of APTMS and poly(PFPA) on the silica particles are confirmed by X-ray photoelectron spectroscopy (XPS), as well as monitored by the particle size change measured via dynamic light scattering (DLS). To improve the surface hydrophilicity of the beads, partial substitution of poly(PFPA) with amine-functionalized poly(ethylene glycol) (amino-PEG) is also performed. The PEG-substituted poly(PFPA) grafted silica beads are then immobilized with antibodies for IP application. For demonstration, an antibody against protein kinase RNA-activated (PKR) is employed, and IP efficiency is determined by Western blotting. The analysis results show that the antibody immobilized beads can indeed be used to enrich PKR while non-specific protein interactions are minimal.

Preparation of Polypentafluorophenyl acrylate Functionalized SiO2 Beads for Protein Purification

A protocol for the preparation of poly(pentafluorophenyl acrylate) (poly(PFPA)) grafted silica beads is presented. The poly(PFPA) functionalized surface is then immobilized with antibodies and used successfully for the protein separation through immunoprecipitation.

We demonstrate a simple method to prepare poly(pentafluorophenyl acrylate) (poly(PFPA)) grafted silica beads for antibody immobilization and subsequent ...

Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids

The epoxidized metabolites of various polyunsaturated fatty acids (PUFAs), termed epoxy fatty acids, have a wide range of roles in human physiology. These metabolites are produced endogenously by the cytochrome P450 class of enzymes. Because of their diverse and potent biological effects, there is considerable interest in studying these metabolites. Determining the unique roles of these metabolites in the body is a difficult task, as the epoxy fatty acids must first be obtained in significant amounts and with high purity. Obtaining compounds from natural sources is often labor intensive, and soluble epoxide hydrolases (sEH) rapidly hydrolyze the metabolites. On the other hand, obtaining these metabolites via chemical reactions is very inefficient, due to the difficulty of obtaining pure regioisomers and enantiomers, low yields, and extensive (and expensive) purification. Here, we present an efficient enzymatic synthesis of 19(S),20(R)- and 16(S),17(R)-epoxydocosapentaenoic acids (EDPs) from DHA via epoxidation with BM3, a bacterial CYP450 enzyme isolated originally from Bacillus megaterium (that is readily expressed in Escherichia coli). Characterization and determination of purity is performed with nuclear magnetic resonance spectroscopy (NMR), high-performance liquid chromatography (HPLC), and mass spectrometry (MS). This procedure illustrates the benefits of enzymatic synthesis of PUFA epoxy metabolites, and is applicable to the epoxidation of other fatty acids, including arachidonic acid (AA) and eicosapentaenoic acid (EPA) to produce the analogous epoxyeicosatrienoic acids (EETs) and epoxyeicosatetraenoic acids (EEQs), respectively.

We present a method useful for large-scale enzymatic synthesis and purification of specific enantiomers and regioisomers of epoxides of arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) with the use of a bacterial cytochrome P450 enzyme (BM3).

The epoxidized metabolites of various polyunsaturated fatty acids (PUFAs), termed epoxy fatty acids, have a wide range of roles in human physiology. These ...

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of functionalized nitrogen-containing target compounds through the regiocontrolled ring-opening of C-substituted aziridines. Despite the tremendous progress in aziridine synthesis over the past decade, accessing contiguous bisaziridines efficiently remains difficult. Therefore, we were interested in synthesizing contiguous bisaziridines bearing an electronically diverse set of N-substituents beyond the single aziridine backbone for regioselective ring-opening reactions with diverse nucleophiles. In this study, chiral contiguous bisaziridines were prepared by organocatalytic asymmetric aziridination of chiral (E)-3-((S)-1-((R)-1-phenylethyl)aziridin-2-yl)acrylaldehyde with N-Ts-O-tosyl or N-Boc-O-tosyl hydroxylamine as the nitrogen source in the presence of (2S)-[diphenyl(trimethylsilyloxy)methyl]pyrrolidine as a chiral organocatalyst. Also demonstrated here are representative examples of regioselective ring-opening reactions of contiguous bisaziridines with a variety of nucleophiles such as sulfur, nitrogen, carbon, and oxygen, and the application of contiguous bisaziridines to the synthesis of multi-substituted chiral pyrrolidines by Pd-catalyzed hydrogenation.

Contiguous bisaziridines containing non-activated and activated aziridines were synthesized by asymmetric organocatalytic aziridinations and then subjected to chemoselective ring-opening reactions under acidic or basic conditions. The non-activated aziridine ring opens with less reactive nucleophiles under acidic conditions, whereas the activated aziridine ring opens with more reactive nucleophiles under basic conditions.

Aziridines, a class of reactive organic molecules containing a three-membered ring, are important synthons for the synthesis of a large variety of ...

Depolymerizable Olefinic Polymers Based on Fused-Ring Cyclooctene Monomers

The growing consumption of synthetic polymers and the accumulation of polymer waste have led to a pressing need for new routes to sustainable materials. Achieving a closed-loop polymer economy via chemical recycling to monomer (CRM) is one such promising route. Our group recently reported a new CRM system based on polymers prepared by ring-opening metathesis polymerization (ROMP) of trans-cyclobutane fused cyclooctene (tCBCO) monomers. This system offers several key advantages, including the ease of polymerization at ambient temperatures, quantitative depolymerization to monomers under mild conditions, and a broad range of functionalities and thermomechanical properties. Here, we outline detailed protocols for the preparation of tCBCO-based monomers and their corresponding polymers, including the preparation of elastic polymer networks and compression molding of linear thermoplastic polymers. We also outline the preparation of high ring strain E-alkene tCBCO monomers and their living polymerization. Finally, the procedures for the depolymerization of linear polymers and polymer networks are also demonstrated.

Here, we describe protocols for the preparation of trans-cyclobutane fused cyclooctenes (tCBCO),&#160;their polymerization to prepare depolymerizable olefinic polymers, and the depolymerization of these polymers under mild conditions. Additionally, protocols for the preparation of depolymerizable networks and compression molding of rigid linear plastics based on this system are described.

The growing consumption of synthetic polymers and the accumulation of polymer waste have led to a pressing need for new routes to sustainable materials. ...

Synthesis of High Purity Nonsymmetric Dialkylphosphinic Acid Extractants

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