We thank Miss. Hirakawa for her great contribution to this research.

NOTE: Please check all related material safety data sheets (MSDS). Please wear protective equipment when experimenting with the copper sulfate plating.
1. Preparation of the copper sulfate plating solution
NOTE: The copper sulfate plating aqueous solution is prepared by combining sulfuric acid (0.5 mol/L), copper sulfate (0.4 mol/L), chlorine (Cl, 1.41 mmol/L), polyethylene glycol (PEG; MW 4000: 0.025 mmol/L), bis(3-sulfopropyl) disulfide (SPS, 0.003 mmol/L), and Janus Green B (JGB, 0.004 mmol/L) in pure water.
<ol>
	<li>Place a stir bar in a 1 L beaker and pour in 600 mL of pure water. Add sulfuric acid (95.0%: 49.04 g) in small portions while stirring. Leave it until the solution cools down.</li>
	<li>Add copper sulfate (99.5%: 99.876 g) to the solution little by little. Stir for 30 min.</li>
	<li>Add 23.7 mL of hydrochloric acid (0.02 mol/L), 0.1 g of polyethylene glycol, 1 mL of 1 mg/L SPS solution, and 1 mL of 2 mg/L JGB solution.</li>
	<li>Transfer the solution to a volumetric flask (1 L). Add pure water and adjust to 1 L. Transfer the copper sulfate plating solution to a polyethylene container and store it at room temperature in the dark.</li>
</ol>
2. Formation of the Cu(I) in the plating solution
<ol>
	<li>Pour 150 mL of the copper sulfate plating solution into a 200 mL beaker. Put the stir bar in the beaker and stir at 500 rpm. Leave the plating solution in advance at room temperature (23 &#176;C &#177; 1 &#176;C) for 1 hour.</li>
	<li>Insert a tube into a beaker and let nitrogen flow (about 85 mL/min). Deoxygenate the plating solution with nitrogen gas for over 30 min.</li>
	<li>Cut the 0.3 mm thick copper plate with metal shears to 9.5 cm x 2 cm dimensions. Cut the platinum plate with a thickness of 0.1 mm in the same way.</li>
	<li>Wash the copper plate and the platinum plate with ethanol and rinse with pure water. Dry with nitrogen gas.</li>
	<li>Attach the copper plate and platinum plate to the fixing jig, insert it inside the beaker and fix it. The immersed area of each plate to the plating solution is 4 x 2 cm2 (See Figure 2). 
	NOTE: The jig consists of an acrylic beaker fixing part (Figure 3 (1)) and metal electrode parts (Figure 3 (2)). The electrode part consists of the parts to fix the plate, and the part connects to the cord from the power supply.</li>
	<li>Connect the electrode (anode) of the copper plate to the positive end of the power supply (Figure 3 (3)), and the electrode of the platinum plate (cathode) to the negative end of the power supply (Figure 3 (4)).</li>
	<li>Turn on the power supply at a constant current of 1.0 A (current density: 62.5 mA/cm2). Cu(I) is formed in the plating solution according to the electrolysis time, and Cu(I) concentration (accumulated amount) is maximized in about 10 min. 
	NOTE: If the plate is inserted while the stirrer rotates, the plating solution may scatter and the beaker may fall over. Please install the jig before turning on the power to avoid danger.</li>
	<li>Turn off the power after 10 min and stop the stirrer. Leave it for about 10 min until the particles settle.</li>
</ol>
3. Quantitative measurement of the Cu(I)
<ol>
	<li>Prepare the BCS solution (10-2 mol/L) by dissolving 0.36 g of the molecule in 100 mL of pure water. Stir the solution and dissolve the BCS in an excess amount relative to the monovalent copper. Store the BCS solution in a light-proof container and store the container in the dark. 
	NOTE: In the measurement, the BCS concentration in the sample solution is adjusted to 1,000 times or more the Cu(I) concentration.</li>
	<li>Add 60 mL of acetic acid (1 mol/L) and 25.2 mL of NaOH solution (1 mol/L) to 120 mL of pure water to prepare a neutralizing solution (buffer solution).</li>
	<li>Put a stir bar in the absorption measurement cell (optical path length: 1 cm) and pour in 2.5 mL of neutralization solution and 219 &#956;L of BCS solution.</li>
	<li>Mix in 22 &#956;L of plating solution sample (step 2.9). Stir for 20 min. 
	NOTE: In order to ensure that the function of BCS is normal, the pH of the sample solution to be measured should not fall below 4. BCS selectively forms a complex with Cu(I). The Cu(I)-BCS complex absorbs in the visible region (400 to 550 nm), and the neutralizing solution develops an orange color (Figure 4).</li>
	<li>Measure the absorption spectra of the sample solution (3.4) with an UV/vis spectrophotometer (wavelength range: 400&#8211;600 nm) (Figure 5e). 
	NOTE: There are no constrained measurement apparatus and conditions, and it is desirable to make them identical in one experiment series.</li>
	<li>Calculate the concentration of Cu(I) using the Lambert-Beer law: 
	A = &#949;lc 
	where A is absorbance, L is the optical path length, &#949; is the molar absorption coefficient (BCS: 1.2 &#215; 104 at 485 nm), and c is the molar concentration (mol/L) of the solute. 
	NOTE: Because the optical path length is 1 cm, the Cu(I) concentration in the cell is simply the absorbance divided by the molar extinction coefficient. The value obtained by multiplying the ratio 125 (the fold dilution with the neutralizing solution) is the Cu(I) concentration of the plating solution.</li>
</ol>
4. Injection measurement of Cu(I) and BCS color reaction curves
<ol>
	<li>Use a UV/vis spectrophotometer with time measurement function of more than 20 min for injection measurement. The spectrometer should have a sample chamber cover with a syringe port (Figure 6 left) and a thermostat cell holder with a stirrer.</li>
	<li>Use a square cell of 1 cm x 1 cm for the absorbance measurement. Put s stir bar in the absorption cell.</li>
	<li>Pour 2.5 mL of the neutralized solution prepared in 3.2 and 219 &#956;L of the BCS solution prepared in 3.1 into the cell. Maximize stirrer rotation speed.</li>
	<li>Set the measurement time to 1,270 s in the time measurement mode at 485 nm and start. One min after starting, inject 22 &#956;L of the plating solution sample (2.9) with a pipette from the syringe port of the chamber cover. Reaction curves of Cu(I) and BCS will be acquired (Figure 6 right).</li>
</ol>

<ol>
	<li>Kondo, K., Akolkar, R. N., Barkey, D., Yokoi, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chap+1.">Chap 1.</a> Copper Electrodeposition for Nanofabrication of Electronics Devices. , (2014).</li><li>Kondo, K., Nakamura, T., Okamoto, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Correlation+between+Cu+(I)-complexes+and+filling+of+via+cross+section+by+copper+electrodeposition.">Correlation between Cu (I)-complexes and filling of via cross section by copper electrodeposition.</a> Journal of Applied Electrochemistry. 39, 1789-1795 (2009).</li><li>Healy, J. P., Pletcher, D., Goodenough, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Chemistry+of+the+additives+in+an+acid+copper+electroplating+bath,+Part+II.+The+instability+of+4,5-dithiaoctance-1,8-disulphonic+acid+in+the+bath+on+open+circuit.">The Chemistry of the additives in an acid copper electroplating bath, Part II. The instability of 4,5-dithiaoctance-1,8-disulphonic acid in the bath on open circuit.</a> Journal of Electroanalytical Chemistry. 338, 167-177 (1992).</li><li>Frandon, E. E., Walsh, F. C., Campbell, S. A. <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+thiourea,+benzotriazole+and+4,5-dithiaoctane-1,8-disulphonic+acid+on+the+Kinetics+of+Copper+Deposition+from+Dilute+Acid+Sulphate+Solution.">Effect of thiourea, benzotriazole and 4,5-dithiaoctane-1,8-disulphonic acid on the Kinetics of Copper Deposition from Dilute Acid Sulphate Solution.</a> Journal of Applied Electrochemistry. 25, 574-583 (1995).</li><li>Gabrielli, C., Mocoteguy, P., Perrot, H., Zdunek, A., Sanz, D. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Model+for+Copper+Deposition+in+the+Damascene+Process+Application+to+the+Aging+of+the+Deposition+Bath.">A Model for Copper Deposition in the Damascene Process Application to the Aging of the Deposition Bath.</a> Journal of The Electrochemical Society. 154 (1), D13-D20 (2007).</li><li>Yokoi, M., Konishi, S., Hayashi, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adsorption+Behavior+of+Polyoxyethyleneglycole+on+the+Copper+Surface+in+an+Acid+Copper+Sulfate+Bath.">Adsorption Behavior of Polyoxyethyleneglycole on the Copper Surface in an Acid Copper Sulfate Bath.</a> Denki Kagaku. 52, 218-223 (1984).</li><li>Pan, S. Z., Song, L. X., Chen, J., Du, F. Y., Yang, J., Xia, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noncovalent+Interaction+of+Polyethylene+Glycol+with+Copper+Complex+of+Ethylenediaminetetraacetic+Acid+and+Its+Application+in+Constructing+Inorganic+Nanomaterials.">Noncovalent Interaction of Polyethylene Glycol with Copper Complex of Ethylenediaminetetraacetic Acid and Its Application in Constructing Inorganic Nanomaterials.</a> Dalton Transactions. 40, 10117-10124 (2011).</li><li>Feng, Z. V., Li, X., Gewirth, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhibition+Due+to+the+Interaction+of+Polyethylene+Glycol,+and+Copper+in+Plating+Bath:+A+Surfce-Enhanced+Raman+Study.">Inhibition Due to the Interaction of Polyethylene Glycol, and Copper in Plating Bath: A Surfce-Enhanced Raman Study.</a> The Journal of Physical Chemistry. B. 107, 9415-9423 (2003).</li><li>Palmer, J. <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+Copper+Species+in+Atmospheric+Waters.">Determination of Copper Species in Atmospheric Waters.</a> The Plymouth Student Scientist. 7 (2), 151-184 (2014).</li><li>Faizullah, A., Townshend, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spectrophotometric+Determination+of+Copper+by+Flow+Injection+Analysis+with+an+On-Line+Reduction+Column.">Spectrophotometric Determination of Copper by Flow Injection Analysis with an On-Line Reduction Column.</a> Analytica Chimica Acta. 172, 291-296 (1985).</li><li>Koga, T., Hirakawa, C., Takeshita, M., Terasaki, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quenching+Characteristics+of+Bathocuproinedisulfonic+Acid,+Disodium+Salt+in+Aqueous+Solution+and+Copper+sulfate+plating+solution.">Quenching Characteristics of Bathocuproinedisulfonic Acid, Disodium Salt in Aqueous Solution and Copper sulfate plating solution.</a> Japanese Journal of Applied Physics. 57, (2018).</li><li>Noma, H., 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=Analysis+of+Cu(I)+in+Copper+Sulfate+Electroplating+Solution.">Analysis of Cu(I) in Copper Sulfate Electroplating Solution.</a> Journal of The Surface Finishing Society of Japan. 63, 124-128 (2012).</li><li>Noma, H., 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=Analysis+of+Cu(I)+Complexes+in+Copper+Sulfate+Electroplating+Solution+by+Using+Reaction+Kinetics+with+a+Chelate+Regent.">Analysis of Cu(I) Complexes in Copper Sulfate Electroplating Solution by Using Reaction Kinetics with a Chelate Regent.</a> ECS Transactions. 58 (17), 77-88 (2014).</li><li>Koga, T., Nonaka, K., Sakata, Y., Terasaki, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrochemical+Formation+and+Accumulation+of+Cu(I)+in+Copper+Sulfate+Electroplating+Solution.">Electrochemical Formation and Accumulation of Cu(I) in Copper Sulfate Electroplating Solution.</a> Journal of The Electrochemical Society. 165 (10), D423-D426 (2018).</li><li>Koga, T., Nonaka, K., Sakata, Y., Terasaki, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spectroscopic+and+Electrochemical+Analysis+of+Cu(I)+in+Electroplating+Solution+and+Evaluation+of+Plated+Films.">Spectroscopic and Electrochemical Analysis of Cu(I) in Electroplating Solution and Evaluation of Plated Films.</a> Journal of The Electrochemical Society. 165 (10), 467-471 (2018).</li></ol>

We have nothing to disclose.

Figure 2 schematically shows a system for electrolysis experiment. The jig is an ordered item, which consists of an acrylic part to be fixed to beakers and metal parts for attaching plates and for connecting with the power supply. By this mechanism, the immersion area of the plates becomes constant, and the relationship between the current value and the current density is kept constant. In our conditions, immersion is 4 cm x 2 cm, and the current density will be 62.5 mA/cm2 with a current of 1 A. In the accumulation procedure of Cu(I), a copper plate is attached to the anode and a platinum plate is attached to the cathode. In order to increase the accumulation efficiency of Cu(I), it is preferable to deoxidize the plating solution with nitrogen gas beforehand.
Quantitative measurement of Cu(I) consists of a simple procedure. Pour the neutralization solution and BCS solution into the cell and mix the plating solution (Figure 4). It is necessary to stir for more than 20 min until Cu(I) and BCS react sufficiently. This is to ensure the accuracy of the measurement by sufficiently advancing the reaction. If Cu(I) is contained in the plating solution, the sample solution appears orange and an absorption spectrum having a peak at 485 nm is obtained. Changes in solution color due to the complex formation were dramatic and surprised many copper plating technicians.
It is confirmed that Cu(I) accumulates in the solution when a current is passed through the copper sulfate plating solution (Figure 5). The absorption spectrum shows the shape of the Cu(I)-BCS complex, which is suitable for calculating the Cu(I) concentration from the absorbance at 485 nm. Although the current value is arbitrary, Cu(I) is hardly accumulated at a current value of 0.2 A, and a higher current value is required. Although the accumulation amount of Cu(I) tends to increase with electrolysis time, it is saturated by excessive current (for example, electrolysis for more than 10 min at 1.0 A). The accumulation amount of Cu(I) increased by electrolysis for 10 min when the current value was 0.5 to 1.0 A14. When an excessive current flowed (for example, at 1.0 A for 20 min), the Cu(I) concentration decreased. This is thought to be related to the formation of copper particles due to the progress of the disproportionate reaction.
The reaction of Cu(I) and BCS in the plating solution has multiple time components, which often make the accurate determination of the concentration difficult. In order to solve this problem, an injection measurement is desirable (Figure 6). In this measurement, the absorption intensity of the Cu(I)-BCS complex is acquired as a changed amount from the baseline before injection of the plating solution, so it can be determined more accurately. In addition, since the reaction curve can be simply numerically analyzed, the concentration can be known with high accuracy even if the reaction is not completed. The components of the reaction curve are thought to reflect the retention structure of Cu(I) in the plating solution14.
It is important to model the holding structure of Cu(I) in the plating solution against the assertion that Cu(I) in the plating bath instantaneously oxidizes Cu(II). We propose the following model from analysis of characteristics of the current amount, formation, and accumulation of Cu(I). A portion of the Cu(I) eluted from the copper plate is retained in solution in the form of a Cu(I)-PEG complex. In early stages of the complex formation, chloride ions are thought to play a role as a temporary stabilizer for Cu(I)6,8. Cu(I) coordinated to PEG is incorporated inside the three-dimensional structure, and it is in a hydrophobic environment. When the formation of Cu(I) is promoted, excess Cu(I) is coordinated to the surface of the PEG and may be in the vicinity of the liquid. Since Cu(I) on the surface reacts promptly with BCS, it will reflect the A0 component of the reaction curve. Since the Cu(I) inside the PEG is protected from BCS attack, it has a slow AL component. It has been pointed out that the A0 component mainly influences the quality of the plating film15. This information is important for management of the plating solution.
By accelerating the denaturation of the plating solution and verifying the accumulated Cu(I) concentration and the holding structure, it is possible to clearly characterize the plating solution. This is important not only for understanding the plating process but also for predicting the quality of the plating film to be produced. From the verification of the SEM image, it was shown that the Cu(I) concentration, especially the A0 component, is strongly involved in the generation of the roughness of the plating film (Figure 8). On-site measurement of Cu(I) gives new indications for the management of plating baths.
This research can contribute to the management of the plating bath based on optical measurement. We aim to develop a system that can evaluate the state of the plating bath on the production line on-time and in situ.

As printed circuit boards become denser and multilayered, management of plating solutions during the manufacturing process becomes more important to maintain product quality. In copper sulfate electroplating, the monovalent copper ion (cuprous ion: Cu(I)) has been determined to be one of the main causes of the large roughness and dull finish of the copper plating surface. The behavior and role of Cu(I) in the plating process1,2,3,4,5, the effect of each additive, and the holding structure6,7,8 have been investigated. It is necessary to analyze Cu(I) in the plating solution, but it was difficult to quantify its concentration because of the instability of Cu(I) in an aqueous solution. Therefore, the on-site analysis of Cu(I) in the plating bath is an effective tool for controlling the plating solution.
We performed colorimetric analysis using an aqueous chelating reagent, BCS (bathocuproinedisulfonic acid, disodium salt), to establish on-site quantitative analysis of Cu(I) in a copper sulfate plating solution. The BCS can be used to quantify the Cu(I) concentration in the aqueous solutions9,10,11. The cuproine type color reaction reagent, which has been conventionally used for the determination of Cu(I), is hydrophobic and extraction with alcohol is necessary. It was shown that BCS is hydrophilic and can directly measure Cu(I) in an aqueous solution. Two molecules of BCS coordinate to one Cu(I) to form 1:2 complexes that absorb visible light at wavelengths between 400 and 550 nm (See Figure 1). We established a method to determine the concentration of Cu(I) in the plating solution from the measurement of the absorbance of the Cu(I)-BCS complex12,13. In the first part of this protocol, a method of accelerating the Cu(I) formation in a copper sulfate plating solution in a model experimental system and the quantitative measurement of the Cu(I) concentration in a plating solution are described. This is fundamental to clarify the process of formation and accumulation of Cu(I) in the plating bath.
Further, it was shown that the color reaction of Cu(I) and BCS can be divided into rapid reaction components and relatively slow reaction components. This increases the uncertainty in the absorbance measurement. To overcome this problem, we developed a method of measuring reaction curves by an injection method14,15. The second part shows the measurement of Cu(I) based on the injection method. By analyzing the components obtained by the injection method, it is possible to approximate the understanding of the Cu(I) formation mechanism and holding structure in solution.
Conventionally, it has been claimed that Cu(I) in a plating solution is instantly oxidized to cupric ions (Cu(II)). We have confirmed that there are several millimoles (mmol/L) of Cu(I) in the plating bath of the production line12. According to this experiment method, the accumulation of Cu(I) similar to the plating bath can be reproduced even in the beaker of the laboratory. This is a fundamental technology to elucidate the Cu(I) production and accumulation process in a copper sulfate electroplating solution, which was unknown14. Furthermore, by controlling Cu(I) in the plating solution, it is also possible to predict the effect of Cu(I) on the quality of the plating film15.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Acetic acid</td>
			<td>Wako</td>
			<td>016-18835</td>
			<td></td>
		</tr>
		<tr>
			<td>BCS</td>
			<td>Dojindo</td>
			<td>B002</td>
			<td></td>
		</tr>
		<tr>
			<td>Copper plate</td>
			<td>YAMAMOTO-MS</td>
			<td>B-60-P05</td>
			<td></td>
		</tr>
		<tr>
			<td>Copper sulfate</td>
			<td>Wako</td>
			<td>033-04415</td>
			<td></td>
		</tr>
		<tr>
			<td>Hydrochorinic acid</td>
			<td>SIGMA-ALDRICH</td>
			<td>13-1750-5</td>
			<td></td>
		</tr>
		<tr>
			<td>JGB</td>
			<td>Wako</td>
			<td>106-00011</td>
			<td></td>
		</tr>
		<tr>
			<td>Magnetic stirrer</td>
			<td>Iuchi</td>
			<td>HS-30D</td>
			<td></td>
		</tr>
		<tr>
			<td>NaOH</td>
			<td>NACALAI TESQUTE</td>
			<td>31511-05</td>
			<td></td>
		</tr>
		<tr>
			<td>PEG4000</td>
			<td>Wako</td>
			<td>162-09115</td>
			<td></td>
		</tr>
		<tr>
			<td>Platinum plate</td>
			<td>NILACO</td>
			<td>PT-353326</td>
			<td></td>
		</tr>
		<tr>
			<td>Power supply</td>
			<td>TAKASAGO</td>
			<td>LX018-28</td>
			<td></td>
		</tr>
		<tr>
			<td>SPS</td>
			<td>Wako</td>
			<td>327-87481</td>
			<td></td>
		</tr>
		<tr>
			<td>Stir bar</td>
			<td>AS ONE</td>
			<td>1-5409-01</td>
			<td></td>
		</tr>
		<tr>
			<td>Sulfuric acid</td>
			<td>Wako</td>
			<td>192-04696</td>
			<td></td>
		</tr>
		<tr>
			<td>Syringe port</td>
			<td>JASCO</td>
			<td>CSP-749</td>
			<td></td>
		</tr>
		<tr>
			<td>Thermostat cell holder with a stirrer</td>
			<td>JASCO</td>
			<td>STR-773</td>
			<td></td>
		</tr>
		<tr>
			<td>UV/vis Spectrophotometer</td>
			<td>JASCO</td>
			<td>V-630</td>
			<td></td>
		</tr>
	</tbody>
</table>

accumulation and analysis of cuprous ions in a copper sulfate plating solution

Knowledge of the behavior of cuprous ions (monovalent copper ion: Cu(I)) in a copper sulfate plating bath is important for improving the plating process. We successfully developed a method to quantitatively and easily measure Cu(I) in a plating solution and used it for evaluation of the solution. In this paper, a quantitative absorption spectrum measurement and a time-resolved injection measurement of Cu(I) concentrations by a color reaction are described. This procedure is effective as a method to reproduce and elucidate the phenomenon occurring in the plating bath in the laboratory. First, the formation and accumulation process of Cu(I) in solution by electrolysis of a plating solution is shown. The amount of Cu(I) in the solution is increased by electrolysis at higher current values &#8203;&#8203;than the usual plating process. For the determination of Cu(I), BCS (bathocuproinedisulfonic acid, disodium salt), a reagent that selectively reacts with Cu(I), is used. The concentration of Cu(I) can be calculated from the absorbance of the Cu(I)-BCS complex. Next, the time measurement of the color reaction is described. The color reaction curve of Cu(I) and BCS measured by the injection method can be decomposed into an instantaneous component and a delay component. By analysis of these components, the holding structure of Cu(I) can be clarified, and this information is important when predicting the quality of the plating film to be produced. This method is used to facilitate the evaluation of the plating bath in the production line.

The concentration of Cu(I) in the plating solution can be determined from the absorbance at 485 nm of Cu(I)-2BCS chelate. Figure 5 shows the absorption spectra of the plating solutions that were electrolyzed for 0, 4, 6, 8 and 10 min. The Cu(I) concentration tends to increase from 0 to 10 min depending on the electrolysis time. However, as a result of the time-resolved measurement, a delay component appeared in addition to the instantaneous component in the reaction between BCS and Cu(I). This reduces the signal-to-noise ratio (S/N ratio) of the absorbance value and prevents accurate determination of Cu(I) concentration. It is preferable to use the injection method to determine the Cu(I) concentration, because the change in absorbance caused by the injection of plating solution is measured by time decomposition (Figure 6).
Information on the Cu(I) holding structure in the plating solution is obtained by numerical analysis of the reaction curve. In general, Cu(I) is quickly oxidized to Cu(II) in an aqueous solution; but in the plating solution it is considered to be stabilized by forming a complex with an additive (especially PEG)14. The reaction curve reflects the chelation process of Cu(I) and BCS. The reaction curve is composed of a component that increases immediately after the plating solution injection and a component that slowly increases over several tens of min. These components suggest that there are multiple holding structures of Cu(I) in the plating solution. Characteristics of the plating solution involved in Cu(I) can be evaluated by analyzing the reaction curve. Assuming that the reaction of Cu(I) with BCS is a first order reaction with respect to the Cu(I) concentration, we obtained the following reaction kinetics of the absorbance, At:
At = A0 + AL [1 &#8211; exp (&#8722;t/TL)]
t is the time from the start of measurement, A0 corresponds to a component that reacts instantaneously (absorbance at t = 0) and AL corresponds to a component that reacts slowly (At - A0). TL is the time constant of the AL component. To simulate the color reaction curve, we applied the formula to the original analysis software (software may be commercially available)13,15. A curve simulating the change in the absorbance of the color reaction of the electroplating solution is shown in Figure 7. From the simulation, the parameters (A0, AL, TL) related to Cu(I) accumulation are quantified. The simulation results in this figure were A0 = 0.053, AL = 0.098, TL = 13.6 min, and r2 = 0.998. Figure 8 (graph) plots the simulation value A0 in the plating solution that was electrolyzed for different times. Although the value of A0 did not change greatly until 4 min of electrolysis, an increase corresponding to electrolysis time was seen from 6 min to 10 min.
Plating was carried out on a copper substrate for 10 min with the electrolysis solutions to investigate the effect of Cu(I) on the quality of the copper plating such as roughness and morphology. Figure 8 shows the SEM (Scanning Electron Microscope) images of the film surface structure deposited with electrolysis solutions. The film structure at 0 min and at 4 min of electrolysis plating are nearly indistinguishable. There are fine particles adsorbed densely with a size of several tens of nanometers and a smooth surface morphology. After 6 min of electrolysis plating, there is some swelling on the surface. After 10 min of electrolysis plating, there is a large chunky roughness.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/59376/59376fig1.jpg" /> 
Figure 1: Structure and absorption spectrum of Cu (I)-BCS complex. Fresh copper sulfate plating solution and electrolysis solution. Since Cu(I) is accumulated in the plating solution by electrolysis, the absorption spectrum of Cu(I)-BCS complex is observed in the electrolysis plating solution sample. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59376/59376fig1large.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/59376/59376fig2.jpg" /> 
Figure 2: Schematic diagram of the equipment for electrification experiment (left) and representative conditions of the electrolysis experiment (right). <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59376/59376fig2large.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/59376/59376fig3.jpg" /> 
Figure 3: Picture of a combinations of parts to be energized in the experiment. Attach the jig with the electrode plate to the glass beaker and connect it to the power supply. (1) Acrylic beaker fixing part, (2) metal electrode parts, (3) copper plate electrode (anode), and (4) platinum plate electrode (cathode). <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59376/59376fig3large.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/59376/59376fig4.jpg" /> 
Figure 4: Absorption measurement of Cu(I). Absorption measurement procedure (left) and photos of sample solution (right). Fresh copper sulfate plating solution (blue) and electrolysis solution (orange). Since Cu(I) is accumulated in the plating solution by electrolysis, it is colored orange in the electrolysis plating solution sample. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59376/59376fig4large.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/59376/59376fig5.jpg" /> 
Figure 5: Absorption spectra of Cu(I)-BCS in electrolysis solutions. Electrolysis time: (a) 0, (b) 4, (c) 6, (d) 8, and (e) 10 min. Since the absorbance of Cu(I)-BCS generally increases as the electrolysis time becomes longer, it is considered that the amount of Cu(I) accumulated in the plating solution is increased. This figure is a modification of Figure 2 of Koga et al. 201815. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59376/59376fig5large.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/59376/59376fig6.jpg" /> 
Figure 6: Injection measurement. Left: Picture of chamber cover. There is a syringe port at the top of the cell; insert a pipette there and inject sample solution. Right: Reaction curve of plating solution which was electrolyzed at 1.0 A for 10 min. A sharp increase in absorbance immediately after injection and a gentle increase are clearly observed. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59376/59376fig6large.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/59376/59376fig7.jpg" /> 
Figure 7: Simulation of absorbance of plating solution (1.0 A, 10 min). <img alt="Equation" src="/files/ftp_upload/59376/59376eq1.jpg" />: measured point, solid line: fitting curve. This figure is a modification of Figure 4 of Koga et al. 201815. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59376/59376fig7large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 8" class="xfigimg" src="/files/ftp_upload/59376/59376fig8.jpg" /> 
Figure 8: Deposition versus electrolysis time. (Graph) Normalized absorbance fitting parameters are plotted against electrolysis time, A0. (Pictures) SEM images of the plating film surface that were deposited in each electrolysis solution (times above pictures are electrolysis times). <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59376/59376fig8large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Accumulation and Analysis of Cuprous Ions in a Copper Sulfate Plating Solution at JoVE.com

Accumulation and Analysis of Cuprous Ions in a Copper Sulfate Plating Solution

Here, accumulation of cuprous ions in a copper sulfate plating solution in a model experiment and an analysis based on quantitative measurements are described. This experiment reproduces the accumulation process of cuprous ions in the plating bath.

Knowledge of the behavior of cuprous ions (monovalent copper ion: Cu(I)) in a copper sulfate plating bath is important for improving the plating process. ...

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14.9K Views.  National Institute of Advanced Industrial Science and Technology (AIST). Here, accumulation of cuprous ions in a copper sulfate plating solution in a model experiment and an analysis based on quantitative measurements are described. This experiment reproduces the accumulation process of cuprous ions in the plating bath.

Video: Accumulation and Analysis of Cuprous Ions in a Copper Sulfate Plating Solution

Activating Molecules, Ions, and Solid Particles with Acoustic Cavitation

The chemical and physical effects of ultrasound arise not from a direct interaction of molecules with sound waves, but rather from the acoustic cavitation: the nucleation, growth, and implosive collapse of microbubbles in liquids submitted to power ultrasound. The violent implosion of bubbles leads to the formation of chemically reactive species and to the emission of light, named sonoluminescence. In this manuscript, we describe the techniques allowing study of extreme intrabubble conditions and chemical reactivity of acoustic cavitation in solutions. The analysis of sonoluminescence spectra of water sparged with noble gases provides evidence for nonequilibrium plasma formation. The photons and the "hot" particles generated by cavitation bubbles enable to excite the non-volatile species in solutions increasing their chemical reactivity. For example the mechanism of ultrabright sonoluminescence of uranyl ions in acidic solutions varies with uranium concentration: sonophotoluminescence dominates in diluted solutions, and collisional excitation contributes at higher uranium concentration. Secondary sonochemical products may arise from chemically active species that are formed inside the bubble, but then diffuse into the liquid phase and react with solution precursors to form a variety of products. For instance, the sonochemical reduction of Pt(IV) in pure water provides an innovative synthetic route for monodispersed nanoparticles of metallic platinum without any templates or capping agents. Many studies reveal the advantages of ultrasound to activate the divided solids. In general, the mechanical effects of ultrasound strongly contribute in heterogeneous systems in addition to chemical effects. In particular, the sonolysis of PuO2 powder in pure water yields stable colloids of plutonium due to both effects.

Acoustic cavitation in liquids submitted to power ultrasound creates transient extreme conditions inside the collapsing bubbles, which are the origin of unusual chemical reactivity and light emission, known as sonoluminescence. In the presence of noble gases, nonequilibrium plasma is formed. The "hot" particles and the photons generated by collapsing bubbles are able to excite species in solution.

The chemical and physical effects of ultrasound arise not from a direct interaction of molecules with sound waves, but rather from the acoustic ...

In Situ SIMS and IR Spectroscopy of Well-defined Surfaces Prepared by Soft Landing of Mass-selected Ions

Soft landing of mass-selected ions onto surfaces is a powerful approach for the highly-controlled preparation of materials that are inaccessible using conventional synthesis techniques. Coupling soft landing with in situ characterization using secondary ion mass spectrometry (SIMS) and infrared reflection absorption spectroscopy (IRRAS) enables analysis of well-defined surfaces under clean vacuum conditions. The capabilities of three soft-landing instruments constructed in our laboratory are illustrated for the representative system of surface-bound organometallics prepared by soft landing of mass-selected ruthenium tris(bipyridine) dications, [Ru(bpy)3]2+ (bpy = bipyridine), onto carboxylic acid terminated self-assembled monolayer surfaces on gold (COOH-SAMs). In situ time-of-flight (TOF)-SIMS provides insight into the reactivity of the soft-landed ions. In addition, the kinetics of charge reduction, neutralization and desorption occurring on the COOH-SAM both during and after ion soft landing are studied using in situ Fourier transform ion cyclotron resonance (FT-ICR)-SIMS measurements. In situ IRRAS experiments provide insight into how the structure of organic ligands surrounding metal centers is perturbed through immobilization of organometallic ions on COOH-SAM surfaces by soft landing. Collectively, the three instruments provide complementary information about the chemical composition, reactivity and structure of well-defined species supported on surfaces.

In Situ SIMS and IR Spectroscopy of Well-defined Surfaces Prepared by Soft Landing of Mass-selected Ions

Soft landing of mass-selected ions onto surfaces is a powerful approach for the highly-controlled preparation of novel materials. Coupled with analysis by in situ secondary ion mass spectrometry (SIMS) and infrared reflection absorption spectroscopy (IRRAS), soft landing provides unprecedented insights into the interactions of well-defined species with surfaces.

Soft landing of mass-selected ions onto surfaces is a powerful approach for the highly-controlled preparation of materials that are inaccessible using ...

Exfoliation of Egyptian Blue and Han Blue, Two Alkali Earth Copper Silicate-based Pigments

In a visualized example of the ancient past connecting with modern times, we describe the preparation and exfoliation of CaCuSi4O10 and BaCuSi4O10, the colored components of the historic Egyptian blue and Han blue pigments. The bulk forms of these materials are synthesized by both melt flux and solid-state routes, which provide some control over the crystallite size of the product. The melt flux process is time intensive, but it produces relatively large crystals at lower reaction temperatures. In comparison, the solid-state method is quicker yet requires higher reaction temperatures and yields smaller crystallites. Upon stirring in hot water, CaCuSi4O10 spontaneously exfoliates into monolayer nanosheets, which are characterized by TEM and PXRD. BaCuSi4O10 on the other hand requires ultrasonication in organic solvents to achieve exfoliation. Near infrared imaging illustrates that both the bulk and nanosheet forms of CaCuSi4O10 and BaCuSi4O10 are strong near infrared emitters. Aqueous CaCuSi4O10 and BaCuSi4O10 nanosheet dispersions are useful because they provide a new way to handle, characterize, and process these materials in colloidal form.

The preparation and exfoliation of CaCuSi4O10&#160;and BaCuSi4O10 are described. Upon stirring in hot water, CaCuSi4O10 spontaneously exfoliates into monolayers, whereas BaCuSi4O10&#160;requires ultrasonication in organic solvents. Near infrared (NIR) imaging illustrates the NIR emission properties of these materials, and aqueous dispersions of these nanomaterials are useful for solution processing.

In a visualized example of the ancient past connecting with modern times, we describe the preparation and exfoliation of CaCuSi4O10 and BaCuSi4O10, the ...

Preparation and Characterization of SDF-1&#945;-Chitosan-Dextran Sulfate Nanoparticles

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under appropriate conditions. The glycan nanoparticles are useful carriers for protein factors, which facilitate the in vivo delivery of the proteins and sustain their retention in the targeted tissue. The glycan polyelectrolyte complexes are also ideal for protein delivery, as the incorporation is carried out in aqueous solution, which reduces the likelihood of inactivation of the proteins. Proteins with a heparin-binding site adhere to dextran sulfate readily, and are, in turn, stabilized by the binding. These particles are also less inflammatory and toxic when delivered in vivo. In the protocol described below, SDF-1&#945; (Stromal cell-derived factor-1&#945;), a stem cell homing factor, is first mixed and incubated with dextran sulfate. Chitosan is added to the mixture to form polyelectrolyte complexes, followed by zinc sulfate to stabilize the complexes with zinc bridges. The resultant SDF-1&#945;-DS-CS particles are measured for size (diameter) and surface charge (zeta potential). The amount of the incorporated SDF-1&#945; is determined, followed by measurements of its in vitro release rate and its chemotactic activity in a particle-bound form.

The objective of this protocol is to incorporate SDF-1&#945;, a stem cell homing factor, into dextran sulfate-chitosan nanoparticles. The resultant particles are measured for their size and zeta potential, as well as the content, activity, and in vitro release rate of SDF-1&#945; from the nanoparticles.

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under ...

Dynamic Electrochemical Measurement of Chloride Ions

This protocol describes the dynamic measurement of chloride ions using the transition time of a silver silver chloride (Ag/AgCl) electrode. Silver silver chloride electrode is used extensively for potentiometric measurement of chloride ions concentration in electrolyte. In this measurement, long-term and continuous monitoring is limited due to the inherent drift and the requirement of a stable reference electrode. We utilized the chronopotentiometric approach to minimize drift and avoid the use of a conventional reference electrode. A galvanostatic pulse is applied to an Ag/AgCl electrode which initiates a faradic reaction depleting the Cl&#713; ions near the electrode surface. The transition time, which is the time to completely deplete the ions near the electrode surface, is a function of the ion concentration, given by the Nernst equation. The square root of the transition time is in linear relation to the chloride ion concentration. Drift of the response over two weeks is negligible (59 &#181;M/day) when measuring 1 mM [Cl&#713;]using a current pulse of 10 Am-2. This is a dynamic measurement where the moment of transition time determines the response and thus is independent of the absolute potential. Any metal wire can be used as a pseudo-reference electrode, making this approach feasible for long-term measurement inside concrete structures.

Dynamic measurement of chloride ions is presented. Transition time of an Ag/AgCl electrode, during a chronopotentiometric technique, can give the concentration of chloride ions in electrolyte. This method does not require a stable conventional reference electrode.

This protocol describes the dynamic measurement of chloride ions using the transition time of a silver silver chloride (Ag/AgCl) electrode. Silver silver ...

Synthesis and Exfoliation of Discotic Zirconium Phosphates to Obtain Colloidal Liquid Crystals

Due to their abundance in natural clay and potential applications in advanced materials, discotic nanoparticles are of interest to scientists and engineers. Growth of such anisotropic nanocrystals through a simple chemical method is a challenging task. In this study, we fabricate discotic nanodisks of zirconium phosphate [Zr(HPO4)2&#183;H2O] as a model material using hydrothermal, reflux and microwave-assisted methods. Growth of crystals is controlled by duration time, temperature, and concentration of reacting species. The novelty of the adopted methods is that discotic crystals of size ranging from hundred nanometers to few micrometers can be obtained while keeping the polydispersity well within control. The layered discotic crystals are converted to monolayers by exfoliation with tetra-(n)-butyl ammonium hydroxide [(C4H9)4NOH, TBAOH]. Exfoliated disks show isotropic and nematic liquid crystal phases. Size and polydispersity of disk suspensions is highly important in deciding their phase behavior.

A two dimensional model material of discotic zirconium phosphate was developed. The inorganic crystal with lamellar structure was synthesized by hydrothermal, reflux, and microwave-assisted methods. On exfoliation with organic molecules, layered crystals can be converted to monolayers, and nematic liquid crystal phase was formed at sufficient concentration of monolayers.

Due to their abundance in natural clay and potential applications in advanced materials, discotic nanoparticles are of interest to scientists and ...

Sulfate Separation by Selective Crystallization with a Bis-iminoguanidinium Ligand

A simple and effective method for selective sulfate separation from aqueous solutions by crystallization with a bis-guanidinium ligand, 1,4-benzene-bis(iminoguanidinium) (BBIG), is demonstrated. The ligand is synthesized as the chloride salt (BBIG-Cl) by in situ imine condensation of terephthalaldehyde with aminoguanidinium chloride in water, followed by crystallization as the sulfate salt (BBIG-SO4). Alternatively, BBIG-Cl is synthesized ex situ in larger scale from ethanol. The sulfate separation ability of the BBIG ligand is demonstrated by selective and quantitative crystallization of sulfate from seawater. The ligand can be recycled by neutralization of BBIG-SO4 with aqueous NaOH and crystallization of the neutral bis-iminoguanidine, which can be converted back into BBIG-Cl with aqueous HCl and reused in another separation cycle. Finally, 35S-labeled sulfate and &#946; liquid scintillation counting are employed for monitoring the sulfate concentration in solution. Overall, this protocol will instruct the user in the necessary skills to synthesize a ligand, employ it in the selective crystallization of sulfate from aqueous solutions, and quantify the separation efficiency.

A protocol for in situ aqueous synthesis of a bis(iminoguanidinium) ligand and its utilization in selective separation of sulfate is presented.

A simple and effective method for selective sulfate separation from aqueous solutions by crystallization with a bis-guanidinium ligand, ...

A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites

The extraction and analysis of catecholamine neurotransmitters in biological fluids is of great importance in assessing nervous system function and related diseases, but their precise measurement is still a challenge. Many protocols have been described for neurotransmitter measurement by a variety of instruments, including high-pressure liquid chromatography (HPLC). However, there are shortcomings, such as complicated operation or hard-to-detect multiple targets, which cannot be avoided, and presently, the dominant analysis technique is still HPLC coupled with sensitive electrochemical or fluorimetric detection, due to its high sensitivity and good selectivity. Here, a detailed protocol is described for the pretreatment and detection of catecholamines with high pressure liquid chromatography with electrochemical detection (HPLC-ECD) in real urine samples of infants, using electrospun composite nanofibers composed of polymeric crown ether with polystyrene as adsorbent, also known as the packed-fiber solid phase extraction (PFSPE) method. We show how urine samples can be easily precleaned by a nanofiber-packed solid phase column, and how the analytes in the sample can be rapidly enriched, desorbed, and detected on an ECD system. PFSPE greatly simplifies the pretreatment procedures for biological samples, allowing for decreased time, expense, and reduction of the loss of targets. 
Overall, this work illustrates a simple and convenient protocol for solid-phase extraction coupled to an HPLC-ECD system for simultaneous determination of three monoamine neurotransmitters (norepinephrine (NE), epinephrine (E), dopamine (DA)) and two of their metabolites (3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC)) in infants' urine. The established protocol was applied to assess the differences of urinary catecholamines and their metabolites between high-risk infants with perinatal brain damage and healthy controls. Comparative analysis revealed a significant difference in urinary MHPG between the two groups, indicating that the catecholamine metabolites may be an important candidate marker for early diagnosis of cases at risk for brain damage in infants.

We present a convenient solid-phase extraction coupled to high-pressure liquid chromatography (HPLC) with electrochemical detection (ECD) for simultaneous determination of three monoamine neurotransmitters and two of their metabolites in infants' urine. We also identify the metabolite MHPG as a potential biomarker for the early diagnosis of brain damage for infants.

The extraction and analysis of catecholamine neurotransmitters in biological fluids is of great importance in assessing nervous system function and ...

DNA-magnetic Particle Binding Analysis by Dynamic and Electrophoretic Light Scattering

Isolation of DNA using magnetic particles is a field of high importance in biotechnology and molecular biology research. This protocol describes the evaluation of DNA-magnetic particles binding via dynamic light scattering (DLS) and electrophoretic light scattering (ELS). Analysis by DLS provides valuable information on the physicochemical properties of particles including particle size, polydispersity, and zeta potential. The latter describes the surface charge of the particle which plays major role in electrostatic binding of materials such as DNA. Here, a comparative analysis exploits three chemical modifications of nanoparticles and microparticles and their effects on DNA binding and elution. Chemical modifications by branched polyethylenimine, tetraethyl orthosilicate and (3-aminopropyl)triethoxysilane are investigated. Since DNA exhibits a negative charge, it is expected that zeta potential of particle surface will decrease upon binding of DNA. Forming of clusters should also affect particle size. In order to investigate the efficiency of these particles in isolation and elution of DNA, the particles are mixed with DNA in low pH (~6), high ionic strength and dehydration environment. Particles are washed on magnet and then DNA is eluted by Tris-HCl buffer (pH = 8). DNA copy number is estimated using quantitative polymerase chain reaction (PCR). Zeta potential, particle size, polydispersity and quantitative PCR data are evaluated and compared. DLS is an insightful and supporting method of analysis that adds a new perspective to the process of screening of particles for DNA isolation.

This protocol describes the synthesis of magnetic particles and evaluation of their DNA-binding properties via dynamic and electrophoretic light scattering. This method focuses on monitoring changes in particle size, their polydispersity and zeta potential of particle surface which play major role in binding of materials such as DNA.

Isolation of DNA using magnetic particles is a field of high importance in biotechnology and molecular biology research. This protocol describes the ...

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the aziridine ring. The utility of bicyclic aziridinium ions, specifically 1-azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted in the aziridine ring openings by the nucleophile with the release of the ring strain to yield the corresponding ring-expanded azaheterocycles such as pyrrolidine, piperidine and azepane with diverse substituents on the ring in regio- and stereospecific manner. Herein, we report a simple and convenient method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate followed by selective ring opening via a nucleophilic attack either at the bridge or at the bridgehead carbon to yield piperidine and azepane rings, respectively. This synthetic strategy allowed us to prepare biologically active natural products containing piperidine and azepane motif including sedamine, allosedamine, fagomine and balanol in highly efficient manner.

Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

Bicyclic aziridinium ions were generated by the removal of an appropriate leaving group through internal nucleophilic attack by nitrogen atom in the ...

Accumulation and Analysis of Cuprous Ions in a Copper Sulfate Plating Solution

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Preparation and Characterization of SDF-1α-Chitosan-Dextran Sulfate Nanoparticles

Dynamic Electrochemical Measurement of Chloride Ions

Synthesis and Exfoliation of Discotic Zirconium Phosphates to Obtain Colloidal Liquid Crystals

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A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites

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