Intelligent flash purification using TLC and MASS spectrometry

Introduction

The compound synthesis, purification and confirmation process often presents challenges throughout. From ensuring successful synthesis of your product, setting up a flash purification method, and finally confirming ID of fractions, the lengthy work flow can be time consuming and repetitive.

This application note demonstrates a new work flow that offers seamless steps to quickly and easily drive the process from reaction monitoring to flash purification and fraction ID.

The three steps that will be highlighted include:

• Step 1: Performing a Suzuki Reaction followed by push-button TLC/CMS analysis with the Advion Plate Express TLC Plate Reader and expression CMS.
• Step 2: TLC to Flash – Purifying the compound using the Interchim puriFlash^® XS520 Flash Chromatography Genius^® system using a method auto-developed from a cell phone image of your TLC plate.
• Step 3: Fraction ID in <30 seconds with the ASAP probe paired with the expression CMS.

 

Experimental setup

Mass Spectrometer & Sampling Techniques:

Advion expression CMS
Plate Express TLC Plate Reader
Atmospheric Solids Analysis Probe (ASAP)

Flash System:

Interchim^® puriFlash^® XS 520

Sample Mixture:

See figure 1

Solvents:

Cyclohexane, 10%
Dichloromethane, 90%

Quantity to purify:

400mg

 

Step 1: Reaction monitoring using TLC

The reaction of Bromoaniline and Phenylboronic acid in ethanol using a palladium catalyst (Figure 1) takes places over a 2-hour period at room temperature. After 2 hours, an aliquot is taken and spotted on a silica TLC plate and developed in Dichloromethane and Cyclohexane solvents.

Chemical	MW	Amount for Reaction
Bromoaniline	171	855mg
Phenylboronic Acid	122	610mg
Sodiumchloride	40	260mg
Paladiumchloride	176	35mg
Ethanol		8mL
Water		2mL
P-Amino-Biphenyl	169	Theoretical: 845mg (5mmol)

Figure 1. The sample mixture including molecular weight, structure and reaction amounts.

 

The reaction is then monitored by TLC/CMS – the Plate Express coupled to the expression Compact Mass Spectrometer for push-button MS analysis of the TLC plate (Figure 2). The system identifies spots unambiguously by taking a mass spectrum directly from the TLC plate (Figure 3).

Figure 2. With the Plate Express TLC plate reader, place the developed TLC and align your spot of interest. At the push of a button, the head lowers and extracts the sample with a solvent to send directly to the mass spectrometer.

 

Figure 3.
Spot 1: The TLC data clearly shows the typical isotopic doublet at an m/z of 172 and 173, the M+H of Bromoaniline, the unreacted starting material.
Spot 2: A MS signal at m/z 170 indicating the desired reaction productp-NH₂-Biphenyl.

 

Step 2: TLC to flash: purifying our compound

The TLC separation information will now be used to intelligently program the Interchim puriFlash system directly from the TLC plate image to give optimal separation for fraction collection. Now that the product is confirmed using the Advion Plate Express, it is prepared for purification using the Interchim^® puriFlash^® XS520. We begin the process by executing an app-the TLC to Flash Converter (Figure 4), giving us the power to purify our compound using our cell phone or tablet.
To do so, the TLC plate is photographed. A title or identification details are entered, the solvent front and product of interest, how much to purify (400mg) and the solvents used (Cyclohexane, 10% and Dichloromethane, 90%). The data is then wirelessly sent to the puriFlash system where the Genius software assists in building the remainder of the method (Figure 5).

Figure 4. With the TLC to Flash app, take a picture of the TLC plate. The compounds will be detected automatically. Select the ones of interest with a tap. The application calculates Rf and ΔCV. Finally, indicate the solvents, their proportions and your comments in the dedicated areas and send to the puriFlash^®.

Figure 5. Les données CCM apparaissent sur le logiciel Intersoft X. Genius l’intelligence embarquée vous suggère la meilleure méthode de purification en fonction de vos données CCM.

 

The screen shows the total UV profile after the run (Figure 6), and using the touch-screen functionality you can find where in the fractions the peaks are located for fraction confirmation analysis in the next step.

Figure 6. La plaque CCM et le profil UV post run.

 

Étape 3 : Identification des fractions en moins de 30 secondes avec l’ASAP/CMS

Flash fractions are located from their UV profile. They need to be confirmed to ensure they have eluted as expected.
We take the central fraction for each compound and analyze them by ASAP/ CMS (Figure 7).

Figure 7. The Atmospheric Solids Analysis Probe (ASAP) is dipped in to one of the identified fraction tubes and inserted in to the mass spectrometer, where is it instantly analyzed by the APCI ion source.

In this fraction (Figure 8) you can again see and confirm using ASAP the signal at m/z 170 indicating the desired reaction productp-NH₂-Biphenyl, which is exactly what we expected.

Figure 8: The data from the run quickly and easily identifies 170 m/z, which is exactly what was expected.

The ASAP sampling technique for the expression Compact Mass Spectrometer is the final step to confirm fractions in seconds by simply dipping the probe in the preidentified tube, and inserting it directly in to the mass spec.

 

Summary

This application work featuring the Advion expression CMS, the Plate Express and ASAP sample techniques, and the Interchim puriFlash flash chromatography system offers easy sampling techniques, intuitive software, and advanced detection technology. Using this streamlined workflow you can easily and confidently synthesize, characterize and purify your compound. The intuitive work flow ensures that:

• The correct TLC spot is identified for purification using the Plate Express and expression CMS.
• An optimized Flash method is recommended and programmed using the Interchim^® puriFlash^® XS520
  and Genius software
• Flash fractions are identified with the ASAP dipping probe and expression CMS

 

Laser Distance Meter Accessories

China leading manufacturers and suppliers of Laser Distance Meter Accessories,Laser Distance Meter Lcd, and we are specialize in Lcd Display,Laser Distance Meter Reflector,Laser Case etc. Those accessories are being a part of Laser products,which play an important role in the whole production line.

About us

1. Quality. Thanks to our strong R&D team, JRT Laser distance meter and modules have been keeping the pace with the measuring technical evolving and pioneering the industry with the unique and patented laser phase measuring solution. From the view of Accuracy, Range, Resolution, Stability, Size and Power Consumption, JRT is undoubtedly one of the best in the line.

2. Schemes of single transmit and single receive. This is one of our patents. We are the only one in the market have this technology. It helps us to reduce our cost and power consumption a lot.

3. Accuracy and Range. Our typical accuracy is ±1.0mm, and range from 40m to 150m.

4. Our laser distance meter and distance module have a high stability, especially for industrial applications.

5. Materials. We use the high performance price ratio components to guarantee the high quality along with a low price.

6. Service. All goods will be inspected and tested before shipment and have one year guarantee and a life-time after sales service. Thirdly, customers` satisfaction is the most important thing to us. If you have any problems or questions, please contact us by Trademanager, email, WhatsApp, Skype, telephone. You will get your respond within 12 hours on working days, 24 hours on holidays.

7. Size. We are keeping research on size of our laser distance module, the smallest size is: 45*25*12mm, 25g for now. We are R&D a new module the size is as small as a pen.

Company Profile

Located in Chengdu, founded at 2004, Chengdu JRT Meter Technology Co., Ltd is a manufacturer and trading company,which is specialized in R&D, processing and selling laser distance meter and modules for 15 years. JRT is one of the leading companies focused on manufacturing laser distance modules in China. We can do OEM designs and make functions as customer required base on our excellent R&D team. JRT is the only factory can make laser distmeters and modules with schemes of single transmit and single receive in china, which greatly reduced our production cost. JRT always make efforts keeping manufacturing laser distance modules cheaper, smaller but with higher quality. Customers` needs are always being the most important things to our company. JRT do its best to make all customer satisfied. To do that, we are keeping improving our quality, service and technology. Making every measurement simple in life is our goal.

Why chose us

Chengdu JRT Meter is the factory of manufacturing laser measure modules sensors more than 14 years.

Supporting OEM your own laser measuring tools.

Welcome to tell us your applicaiton, we are glad to help.

Industial Applicaiton:
1. Distance optional: 40m, 60m, 100m, 120m, 150m
2. Interface optional: serial port, USB, RS232, RS485, Bluetooth etc
3. Operating temperature: -10 ºC~50 ºC can be customized.

FAQ

Q1: What`s the delivery time after an order placed for this Handheld Laser Distance Meter?

A1: Our standard delivery is 3 days if we have stock, otherwise we will let you know in time, usually we manufacture 2000pcs a day.

Q2: What`s the MOQ?

A2: Regular products only 1pcs, OEM/ODM products need 1000pcs at least

Q3: What`s the warranty of the meter?

A3: All our products have one year guarantee and a life-time after sales service.

Q4: Can I have a sample for testing?

A4: Yes. We do not offer free samples, but will reimburse the buyer once an order is confirmed.

After-sales Service

1. All goods will be inspected and tested before shipment.

2. Customers` satisfaction is the most important thing to us. If you have any problems or questions, please contact us by Trademanager, email, WhatsApp, Skype, telephone. You will get your respond within 12 hours on working days, 24 hours on holidays.

Laser Distance Meter Accessories,Laser Distance Meter Lcd,Lcd Display,Laser Distance Meter Reflector

Chengdu JRT Meter Technology Co., Ltd , https://www.jrt-measure.com