YMC – Micro-reactors significantly improve synthesis results

What are the reasons behind the fact that micro-reactors will often achieve better results than conventional reactors? In order for a chemical reaction to run in the optimal manner, several prerequisites have to be met:-

Firstly, near perfect mixing of the reactants has to be achieved, whilst ensuring a large phase transition area in reactions where more then one phase is present. Next, the time needed for the reaction to take place has to be guaranteed by a residence time loop. This is chosen to provide a residence time with as narrow as possible distribution. In addition any reaction heat needed or produced during the process has to be added or removed, respectively. That this is possible has been shown in many very different, reactions. Micro-mixers for liquids provide mixing times in the region of 1s – 1 ms, which are well below those of conventional mixers. As a result intensive mass transport is achieved, which significantly lowers reaction times and increases yield per volume and time. At the same time the surface/volume ratio raises to several 10,000 compared to only about 1-10 for stirred tank reactors (STR). If a micro-heat exchanger is integrated into the micro-reactor, both effects (high mass transfer and high surface/volume ratio) are combined with rapid heat transfer to or from the reactor. In practice heavily exothermal reactions such as chlorination, oxidation, nitration and even fluorination with elemental fluorine (in metal microreactors) can be performed under almost isothermal conditions. Also from the point of view of process safety micro-reactors, which are run in continuous mode, are much superior compared to STR’s, which have to be run in discontinuous mode. Whilst continuous mode operation guarantees that no harmful side products can accumulate they are also easier to control compared to discontinuous ones.

Finally, micro-reactors pose a much lower safety risk, even if, despite all the safety measures incorporated, a run away should occur, simply because of the low volumes if materials involved.

The above holds true for laboratory scale systems, but before using micro-reactors for production scale, several other parameters have to be considered, such as the back pressure generated by the micro-structures involved. These can result in a limitation of the throughput achievable with each micro-reactor module. Micro-reactors are exceptionally well suited for the production of small to medium sized quantities of product, such as frequently required in the fields of active pharmaceutical ingredient or fine/speciality chemicals production. In order to rate different reactions, process stages are normally categorised according to their reaction rate:

• Fast reactions, finished in one second or less need fast mixing of the reactants, furthermore, these reactions, if exothermal, also need fast removal of the reaction heat produced. Both requirements can be fulfilled by using micro-reactors, and their use can optimise the performance of such reactions.


• Reactions taking between one second and ten minutes may also benefit from the use of micro-reactors. In this case, the overall reaction is no longer governed by the mixing, but via the kinetics of the reaction. These cases still require optimal mass and heat transfer combined with improved control of the residence time to allow higher yields and better selectivity. Of course it is necessary to allow these slower reaction rates in the system by addition of residence time loops into the apparatus.


• Slow reactions taking 10 minutes and more are predestined to be performed in STR’s. Using micro-reactors for these reactions can lead to improved process safety, but would demand residence time modules that are so large that the process becomes inefficient. Therefore use of micro-reactors for such reactions is only viable in some exceptional cases.

KeyChem-Basic

KeyChem-L

YMC offers an extensive range of modular systems suitable for the first steps in the laboratory, up to production of amounts of several grams or even kilos. We support novices in their use, as well as experienced users with the implementation of new synthesis strategies and targeted “proof of concept” studies. Initial experiments to get an understanding in the field are performed easily and fast using the KeyChem basic system. KeyChem basic modules offers a number of software controlled systems with extensive data logging possibilities and a wide range of reactors and accessories. The Cytos 200 and Cytos 2000 ranges make the transition to pilot and production scale easy.

CYTOS 200

CYTOS 2000

Customized

The choice of reactors is based on the requirements of the reaction to be performed and the way the user wants to operate the system. The liquid handling modules are independent of the reactors and have to match the chosen reactor. For liquid media, these range from analytical HPLC pumps up to high pressure-resistant precision syringe pumps. Such syringe pumps make it possible to continuously pump liquid, in nanolitre quantities, against high pressures. These pumps are also robust and stable under high pressure conditions, as when using viscous reactants.

Different mixer and dwell modules from microlitre up to high volume millilitre modules are available with different geometries. By including innovative Peltier-technology, KeyChem systems can be cooled and heated without the need for any external heating media.

YMC micro-reactors contribute to the concept of “green chemistry”, as they allow users to find synthesis and production procedures which save resources. These can then be used in production process.

We are happy to answer your questions or to demonstrate the equipment. Please feel free to call us for a tentative offer today

YMC-Triart

• Versatility: balanced hydrophobicity and silianol activity.
• Flexibility: broad pH-range pH 1 - 12
• Extended column life time = Increased productivity!

In addition, the multi-stage endcapping, used for the very first time in stationary phase design, results in outstanding peak shapes being obtained even for basic compounds!

The innovative endcapping process also allows very high MS-sensitivity to be obtained; YMC-Triart is an excellent first choice for residue analysis.

Column: 5 μm, 50 x 2,0 mm ID Eluent: A) water / formic acid (100/0.1) B) acetonitrile / formic acid (100/0.1) 5% B (0-1 min), 5-100% B (1-5 min), 100% B (5-10 min), 100-5% B (10-10.1 min), 5% B (10.1-12.5 min) Flow rate: 0.4 ml/min Temperature: 40 °C Detection: ESI positive, TIC (Mass Range: 50-1000)

Column bleeding, caused by the fragments of stationary phase, is the main reason for background noise and limitations on detection limits. No bleed is observed in the test of total ion current (TIC) measured by LC/MS with blank or with YMC-Triart C18. So in terms of the signalnoise ratio (S/N ratio), YMC-Triart C18 can be expect to not only reduce the background noise but to also increase the sensitivity of the analysis.

Why not try YMC-Triart today!

„Connectivity and Compatibility“ of Kronlab laboratory glass columns

Sometimes one does not see the woods from the trees – or in other words: for some people it is evident, but not so for the others, …

With regards to Kronlab glass columns there are two questions still frequently asked:

Question 1:
What resins may I use in combination with Kronlab glass columns?

Antwort:
In principle, the columns are compatible with any material of any given producer. The only points to
keep in mind are application specific considerations like those concerning compatibility to the materials of
the wetted parts and the pressure limits of columns and packing materials. To accommodate these
Kronlab offers a wide range of columns with different materials and stabilities. YMC’s application laboratory
has a long list of applications covering the areas: ion exchange (IEX), size exclusion chromatography (SEC),
normal/reversed phase, affinity chromatography, etc.
using media of YMC, GE, Pall, BioRad, Tosoh to name only a few references.

Question 2:
Is it possible to connect Kronlab-glass-columns to every LC-equipment or am I limited to Kronlab equipment?

Answer:
Naturally we are happy to see Kronlab-glass-columns being used together with Kronlab equipment, however limitations as to which equipment to use do not exist. The Kronlab laboratory scale glass columns are shipped with a set of connectors to connect to LC-systems of any major supplier (e.g. GE Äkta). Additionally we offer all kinds of special accessories. One example are the yellow connectors shown in the pictures, which make it possible to change from metric to inch connections (i.e. M6 to ¼-28).

Kronlab-lab-glass columns in a „multi-purpose“ contract laboratory
(picture by courtesy of InVivo BioTech Service GmbH)

Our distributor as well as our staff at our head quarter in Germany are happy to answer your questions or to
discuss your particular technical challenge.

BioProcess™ International 25% discount with YMC

YMC has teamed up with Informa, the makers of BioProcess International, to give all YMC customers the opportunity to save 25% on the published conference fees.

YMC will present more details on the BioPro Ion Exchange (IEX) bulk material at the conference. Strong anion and strong cation exchanges with particle sizes of 30 μm and 75 μm are already available and the range of phases is constantly expanding.

Clients are enthusiastic about the extremely high quality of the material. The 75 μm, 100 nm capture material is ideal for high speed capture steps. Its excellent dynamic binding capacity (> 210 mg BSA/ml resin) even at high flow rates of up to 1000 cm/h can improve process efficiency significantly.

The 30 μm, 100 nm BioPro IEX material boasts high resolution of bio-molecules at surprisingly low backpressures and very economic prices.

For 30 years, YMC has been a partner for the pharmaceutical industry. Our experience is your advantage, with full regulatory support on all BioPro IEX materials (incl. DMF and RSF).

Visit our poster or meet us at our booth to discuss your particular (bio)-processing requirements!

You can claim your 25% discount on the conference fees by quoting the
YMC VIP code: CQ3408YM when booking. Find more information via the link below or on
the website: www.bpi-eu.com

19-20 May 2010 • Reed Messe Wien Congress Center, Vienna, Austria

1 EVENT - 5 CONFERENCES - 6 STRATEGIC DISCUSSION FORUMS
PAY ONE PRICE: ATTEND FIVE EVENTS

1 Scale-up, Economics, Manufacturing Strategies and QbD
2 Cell Culture and Upstream Processing
3 Recovery and Purification
4 Formulation Strategies
5 Analytical Methods

You can register for the event online at: http://www.bpi-eu.com/register.cfm

Alternatively, you can book your place through one of the following ways:

Phone Informa’s reservation line on: +44(0) 20 7017 7481
Email: registrations@informa-ls.com
Fax: your completed booking form to: +44 (0) 20 7017 7823
Mail to: The Bookings Department, Informa UK Ltd, P O Box 406, Byfleet, KT14 6WL

In any case, be sure to quote the VIP code mentioned above to claim your 25% discount.
(Feel free to forward this code to your colleagues)

If you are unable to attend, but still want information on the BioPro IEX resins or a sample of the material(s), please feel free to contact us.

Or, why not use the

Analytica 2010

Analytica 2010 took place from 23rd to 27th March in Munich. YMC attended this exhibition with a whole range of new products.

Although the numbers of visitors who met us was slightly down on previous years, the quality of the enquiries was significantly greater. This not only met, but surpassed our expectations and made the show even more successful for us than the 2008 event.

These products were exhibited alongside our full range of YMC HPLC columns, a wide assortment of HPLC accessories, as well as our Kronlab glass columns.

You didn’t have the chance to visit us at the show? No problem!

Just make an appointment with one of our field sales staff or your local distributor, who will take time to show you those products you are interested in.

Your YMC-Team!