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Interest in photochemistry has been growing exponentially in recent years. Numerous new applications using visible-light photoredox catalysis have been discovered. These catalytic systems can perform many types of bond formations using various substrates which are valuable new tools for synthetic chemists.
However photoredox chemistry setup necessitates to the use of a light source (blue light) and apparatus that are not standard yet in an organic chemistry laboratory. Many chemists have made their own setup and tried to reproduce literature chemistry with more or less success. As a result the implementation of photoredox chemistry is slow and organic chemists are still hesitant to try these important new tools. Therefore, the need for a simple and robust device to perform visible-light photoredox catalysis has become increasingly important.
The EvoluChem™ PhotoRedOx Box was designed with one main objective: To allow any chemist to easily perform multiple photoredox reactions in a reproducible environment. Our photochemistry device provide an even light distribution to all reaction samples allowing consistent and reproducible reactions. A cooling fan allows even temperature distribution and keeps the chamber near room temperature during long reaction runs. The device easily fits on standard stir plates, allowing for consistent stirring. Sample holders are compatible with vials ranging from 0.3 ml to 20 ml vials.
The PhotoRedOx Box is using a unique geometry of mirrors to irradiate multiple samples simulatanously for parallel chemistry setup while limiting the thermal effect of the light source. This design results into a compact and efficient photoredox device which can be easely set on any standard stir plate.
The removable lamp adapter allows easy switching from the standard kessil™ blue 34W LED lamp to many other light sources.
Organic chemists needs to be able to use different reaction vial sizes depending on the scale and the number of the reaction to be performed. The PhotoRedOx Box can virtually fit any type of vials including 0.3ml crimped vials (6 x 32mm), 2ml HPLC vials (12 x 32mm), 1DRAM (15 x 45mm), Microwave vial 2-5mL (17 x 83mm), 2DRAM (17 x 60mm) and 20ml scintillation vials (28 x 61mm).
This feature allows quick and consistent scale up from screen reactions to larger scale with preset sample positions removing the guess work on sample placement distance from the light source. When using 0.3 ml vials, 32 reactions can be performed in parallel in the photochemical device. At 20 ml, two reactions can be run in duplicate.
With the EvoluChem photomethylation kit, we have demonstrated the reproducibility of both the photomethylation kit and the device. Using a photomethylation of buspirone as test reaction, 16 vials spread through the 0.3 ml vial sample holder for Trial #1 results in 53% (+/-2 %) conversion. See figure. For a second trial with 16 reaction vials we observed an average conversion of 56% (+/-2 %) for the mono-methylated product.
Each reaction vial contains Ir(dF-CF3-ppy)2(dtbpy)[PF6] (0.1 μmol), tert-butylperacetate solution (12.5 μmol) and a stir bar sealed under inert atmosphere. To each vial was added 50 μl of 0.05 M buspirone solution in 1:1 trifluoroacetic acid/acetonitrile sparged with nitrogen stream. Reaction mixture irradiated with Kessil 34 W blue LED for 18 hr using EvoluChem photochemical device.
The common limitation to scaling up photoredox chemistry is due to the low penetration of the light in to the reaction mixture (few mm) which prohibits the use of large reaction vessels. Surface area is key to shorten reaction time. It is possible to significantly increase the surface area by running the reaction in flow. This will decreases the reaction time and allows to be run in continuous mode for scale-up.
To solve this challenge, we designed a flow reactor that can be used in the PhotoRedOx Box. This flow reactor is using PFA tubing and has volume of 2 ml. Comparing reactions in flow and in batch we observed significant decrease in reaction time.
In a 4-ml vial equipped with a Teflon septa were weighed NiCl2-dme (1.1 mg, 5 μmol, 0.05 mol %) and dtbbpy (1.3 mg, 5 μmol, 0.05 mol %). 1 ml of dry MeOH was added to the vial and the vial was stirred on an orbital shaker until complete dissolution. The solution was evaporated to dry at room temperature. Then Ir(dF-CF3-ppy)2(dtbpy) (1.1 mg, 1 μmol, 0.05 mol %), and 4-bromoacetophenone (9.95 mg, 100 μmol, 1 equiv.) were added. 1 ml of dry acetonitrile was added followed by Et3N (21 μmol, 300 μmol, 3 equiv.) and aniline (4.65 mg, 100 μmol, 1equiv.). The solution was sparged with nitrogen via submerged needle for 5 minutes.
Several batches of 100 μl of solution were successively injected to the flow reactor placed in EvoluChem PhotoRedOx Box with blue Kessil LED using an injection module (Gilson) and the samples were circulated using a HLPC pump at different flow rates to allow residence time of 5, 10, 15, 20 and 30 min. Reaction completion was monitored by LC-MS using the ratio bromoacetophenone/product.
In a 4-ml vial equipped with a Teflon septa were weighed NiCl2-dme (1.1 mg, 5 μmol, 0.1 mol %) and dtbbpy (1.3 mg, 5 μmol, 0.1 mol %). 1 ml of dry MeOH was added to the vial and the vial was stirred on an orbital shaker until complete dissolution. The solution was evaporated to dry at room temperature. Then Ir(dF-CF3-ppy)2(dtbpy) (1.1 mg, 1 μmol, 0.1 mol %), and 4-bromoacetophenone (4.98 mg, 50 μmol, 1 equiv.) were added. 1 ml of dry acetonitrile was added followed by 2,6 lutidine (17.5 μmol, 150 μmol, 3 equiv.) and potassium benzyltrifluoroborate (9.90 mg, 50 μmol, 1 equiv.). The solution was sparged with nitrogen via submerged needle for 5 minutes.
Several batches of 100 μl of solution were successively injected to the flow reactor placed in EvoluChem PhotoRedOx Box with blue Kessil LED using an injection module (Gilson) and the samples were circulated using a HLPC pump to allow residence time of 30 min. Reaction completion was monitored by LC-MS using the ratio bromoacetophenone/product.
Acces directly to our products dedicated to PhotoRedox on our website.
In recent years photoredox chemistry has become a powerful tool for chemical synthesis. Many reactions conditions have been reported in the literature using a wide range of catalysts and reagents. However, often these reactions are highly substrate, solvent and base specific. In order to facilitate the screening of common photochemistry reactions, HepatoChem has released a series of kits combining common Iridium, Nickel, ligand and base combinations to achieve successful cross-coupling transformations.
Depending on the ligand, base and solvent, the Ir/Ni catalytic systems can perform different cross-coupling reaction.
5 µmol of substrates in 100 µl solvent with Ir catalyst (2 mol %), NiCl2•dme (10 mol %), ligand (10 mol %), and 3 equivalent of base.
The art of chemical synthesis continues to evolve through innovation in instrumentation, Interchim works with many companies to offer this enabling technology to leading research scientists across Europe.
One such technology is continuous flow chemistry, and in this area, Interchim collaborates with Uniqsis, a market leader in meso scale flow chemistry. This is a complementary technique to batch and microwave for seamless reaction optimisation, synthesis and scale-up from milligrams to 10 Kg per day.
Interchim offers a wide range of flow chemistry products to make this technique accessible to novices while at the same time catering for complex multi-step fully automated reactions sequences for library synthesis.
To give you an idea on how to minimise risk associated with hazardous intermediates with a small reactor volume, we describe a Curtius Rearrangement carried out with a The FlowSyn™.
The Curtius rearrangement is a useful reaction in synthesis that converts carboxylic acids into their corresponding reversed amino derivatives.
However, the reaction requires the formation of potentially explosive acyl azides as the precursor to isocyanates that undergo nucleophilic attack to afford the reaction products. Under conventional ‘batch’ conditions, the scale of the reaction is therefore often limited for safety reasons. This can present a bottleneck in terms of scale-up.
Flow chemistry offers an attractive alternative whereby the acyl azide intermediate is continuously processed through to product, preventing its accumulation.
System solvent: Acetonitrile.
Stock solution A: 4-Nitrobenzoic acid (925 mg; 5.05 mmol), triethylamine (1.40 mL; 10.0 mmol) and allyl alcohol (1.02 μL; 15.0 mmol) in MeCN (50 mL).
Stock solution B: Diphenylphosphorylazide (DPPA: 1.10 mL; 5.1 mmol) in MeCN (50 mL).
A 100 psi chemically inert fixed back-pressure regulator was fitted and used in all experiments.
FlowSyn™ is equipped with a program that allows unattended operation and is able to run a flow experiment automatically, stopping and cleaning the instrument when the reaction is complete.
1- FlowSyn™ was fitted with a 14 mL HT PTFE tubing reactor cassette, and the heating unit was tensioned to ensure optimal thermal contact.
2- A 10 cm x 15 mm Column reactor was filled with a [1:1] mixture of Amberlyst A-21 and Amberlyst H-15 resins, and the ‘Col Vol’ was set to 3.0 mL in the Configuration Screen.
3 – A 100 psi fixed BPR was connected in-line to the outflow from the tubing reactor before the collection valve.
4 – The pumps and inlet lines were primed.
5 – The following flow parameters were entered into the ‘Auto Set Up’ screen.
6 – Upon pressing ‘Run Experiment’, FlowSyn™ equilibrates to the set temperature and then runs the flow experiment, before finally cleaning the system by flushing with system solvent (‘Wash’).
7 – The collected product solution was concentrated in vacuo to leave allyl-4-nitrophenyl carbamate as a white solid (198 mg; 88%).
UVLC-MS (ESI +ve): (m/z 223.1 (MH+)); Rt = 3.60 min, >99%;
IR (ATR): 3380 (s), 1730 (s),1685 (m), 1610 (m), 1600 (m), 1545 (s), 1508 (s), 1495 (s), 1320 (s), 1305 (s),1205 (s), 1110 (s), 1050 (s), 945 (s), 850 (s), 765 (s), 750 (s), cm−1.
1H NMR (d3-MeCN, 400 MHz): dH 8.28 (1H, s), 8.15 (2H, d, J = 9.2 Hz), 7.65 (2H, d, J = 9.2 Hz), 5.98 (1H, dt, J = 17.3, 10.2, 5.8 Hz), 5.40 (1H, ddt, J = 17.2, 1.6, 1.6 Hz), 5.30 (1H, ddt, J = 10.8, 1.6, 1.6 Hz), 4.65 (2H, d,J = 5.6 Hz)
In this specific case flow chemistry is an excellent alternative to push back the limits of the conventional batch chemistry and to overcome a bottleneck in terms of scale-up.
With our range of flow chemistry systems, we offer modular starter systems to fully integrated fully automatic system.
The FlowLab can offer up to 3 reagent channels, 2 reactor stations and has its own software program for single experiments. It also has the option for an inline UV/VIS detector system to see when the reaction has reached steady state.
All of the reagent have been specially designed for flow chemistry and can deliver 10 ml/min or 50 ml/min with the prep heads at up to 100 bar. Reactions can be carried out in the range -85°C to 300°C.
Purification by liquid chromatography is always a challenge and there is often a compromise to obtain the desired purity, loading and throughput.
To improve efficiency in delivering pure compounds, chemists may balance between purity, run time and environmental considerations.
This delicate balance is often necessary for both crude and final purification.
The Ultra Performance Flash Purification (UPFP) concept achieves accelerated throughput by reducing the time and cost per sample of the purification process with increased confidence. What differentiates UPFP from Flash chromatography is the combination of advanced machine technology, built to last and mastery of small particle spherical silica puriFlash® columns which offers significant benefits over the traditional flash grade silica.
A 15µSIHP-F0040 column gives a better result with greater resolution, efficiency, loading capacity and improved retention versus a IR-50SI column.
Using a 15µSIHP, reduce run time by 45%, improve in time for the purification by 114%, reduce the solvent consumption by 59% and improve in cost for the purification by 26%. Lower collection volume means a decrease of the evaporation time.
If the sufficient selectivity is reached, the 15µSIHP allows to achieve greater fraction purity. The best ratio cost/productivity is obtained with 15µm silica.
Whatever the field of application, pharmaceutical, environment, agro-food, cosmetics, …, a question appears regarding the HPLC or UHPLC analysis of polar compounds: which column to choose?
Today, there are a lot of C18 bonded analytical columns available for the separation of non-polar molecules. With Core Shell or totally porous silica, conventional C18 phases provide a good insight into this analytical problem.
It is the same for Interchim’s C18 AQ stationary phases, which behave with hydrophobic compounds in a similar manner to the traditional C18 stationary phases.
For the analysis of more polar molecules, several questions arise during an analytical method development:
Interchim’s C18 AQ stationary phases present a wider application field than conventional C18 phases.
It is not recommended to use mobile phases containing more than 95% water with a conventional C18. Beyond this value, the C18 chains curl towards the surface of the silica, which has for consequence a loss of retention and separation of the analytes.
The Interchim C18 AQ bonding technology ensures a column that provides perfect repeatability of retention times under 100% aqueous mobile phase conditions.
Under 100% H2O conditions, an increase in retention of the analytes is observed with Interchim C18 AQ phases.
Thanks to their end-capping technology, they provide specific polar selectivities that conventional C18 sorbents do not have.
Separation of very poorly retained products are achieved with Interchim’s C18 AQ bonded silicas where conventional C18 phases fail.
C18 AQ stationary phases provide :
This is why Interchim C18 AQ stationary phases are first choice columns, from analytical scale to purification, from Core-Shell particles to Preparative, an unique offer on the market.
More information :
Download or consult our detailed documentation on the stationary phases C18 AQ from Interchim
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The EvoluChem™ kits are chemistry screening kits. They are the ideal tools for the investigation of chemical reaction conditions. These kits enable you to conveniently screen multiple reaction conditions simultaneously using pre-weighed catalysts and reagents. Most of our kits contain all reagents required to perform the reaction conditions.
The Suzuki-Miyaura coupling kits are ideal tools for the investigation of chemical reaction conditions. These kits enable you to conveniently screen multiple reaction simultaneously using pre-weighed catalysts and reagents. The kit contains all reagents to perform the reaction conditions.
Substrates solution at 0.15M concentration with 10% catalyst, 2 equivalents of base. 100 µl reaction volume. Additional conditions can be investigated by changing substrate concentration, amount of base.
HCK1003-01-001: Includes 1 set of reagents and solvents with 6 catalysts & 4 bases
HCK1003-01-002: Includes 1 set of reagents and solvents with 8 catalysts & 4 bases
Kit contents: 4 reaction vials of each catalysts, 4 bases in aqueous solution at 1M concentration and 4 solvents.
Catalysts available: Pd(PPh3)4, Pd(dppf)2Cl2, PdOAc2/SPhos, PdOAc2/XPhos, Pd2(dba)3/SPhos, Pd2(dba)3/ XPhos, PdOAc2/CataCXium® A and Pd(Amphos)Cl2
Bases: 1M aqueous solutions of Na2CO3, K2CO3, K3PO4 and Cs2CO3
Solvents: Dioxane, n-Butanol, DMF and acetonitrile (sparged with Argon)
Test reaction has been performed using 4-methoxyphenylboronic acid and 4-bromoacetophenone as substrates.
Prepare required volume of a 0.15 mol/L solution of combined substrates (of 4- methoxyphenylboronic acid and 4-bromoacetophenone) in dioxane.
Using a clean and dry syringe, add 100 µl of substrates solution to a reaction vial and mix with the catalysts using the syringe.
Add 30 µl of the selected base solution. (2 equivalents)
Stir the reaction vials in the reaction block at 80° C for 5 hours. Remove the vial caps using a decapper.
Prepare analytical sample for each reaction condition with 5 µl sample diluted into 200 µl in DMSO . Analyze resulting analytical samples by LC/MS
Protein purification looks simple. For a Histidine or a GST tagged protein as well as for an Immunoglobulin one single affinity step followed by a polishing step is enough to get a pure protein. For all the other proteins it is much more complex. The CEP (Capture – Enhance – Polishing) strategy is a key to solve your purification problem.
For a top level purification some key points have to be kept in mind :
Prior any proteins purification we have to keep in mind the proteins could lose their activity entirely or partly. This is due to:
To minimize these risks, we have to avoid :
and we have to :
Following the future use of the protein purifications strategy are different
Following the proteins quantity needed purification tools are different
All the purification technics are usable since all the proteins own negatively charged portions, positively charged portion, hydrophilic, hydrophobic and affinity zones.
1/ Defining the goal
3/ Analytical conditions to develop
3 purification steps must be a maximum. If more, we lose too much target protein. The ratio Purity/cost is no more acceptable.
“Don´t waste clean thinking on dirty enzymes” Efraim Racker
Keep it simple!
In the Bio-Works CEP strategy the planning will define precisely the purification way of the starting material:
The different development steps are used to validate the purification technics, the purification resin and to optimize the protocol (pH, Ionic force, temperature, linear flow rate…)
Know more :
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