Optimization

The goal of Apeiron’s team from day-one has been to work closely with customers to help transform chemistry and bring about a revolution in catalysis and synthesis for R&D pipelines and manufacturing processes.

With the ability to fine-tune selectivity, activity and stability with unparalleled precision, regardless of the application, Apeiron is the right partner to deliver catalysts that contribute tangibly to value creation. By enhancing both the efficiency and yields of your chemical processes, our catalysts help to produce larger quantities of the desired product in a shorter time-frame, making a significant difference in reducing manufacturing costs, while compressing schedules, lowering energy demand and minimizing resource consumption. Apeiron offers extensive technical support, using high-throughput experiments and catalyst optimization to rapidly identify the most suitable catalyst with the optimal performance for your particular application.

Optimization of reactions conditions

1. Nitro-Grela in Pharmaceutical Developement

Challenge: The efficiency of olefin metathesis catalysts is often compromised by certain functional groups that may be present in the substrate, solvent or in trace reaction impurities. For example, Lewis bases can coordinate to the metal center of the active catalytic species, trigger its decomposition, or form a chelating ligand, reducing catalyst turn-over number. A common means to overcome such interference is to increase catalyst loading. However, while this seemingly obvious strategy might work for a one-off, small scale reaction, it is an unsustainably expensive solution for larger scale and decidedly not compatible with commercial processes.

2. Increasing catalysts stability

Challenge: Ring closing metathesis (RCM) reactions of terminal olefins evolve ethylene as a byproduct. The released ethylene generally needs to be eliminated from the reaction mixture to enable optimum efficiency and product yield. If not eliminated, ethylene may take part in unproductive metathesis by entering the catalytic cycle in place of the substrate olefin. This competition can dramatically impact the catalyst’s maximum turn-over-number and induce faster decomposition of the catalyst. Large scale, batch olefin metathesis processes often suffer reduced process efficiency due to inefficient removal of ethylene from the reactor – a potentially serious problem that can force a work-around effort in commercial applications.

 

3. High value chemicals from natural oils

Challenge: Recent advances in ethenolysis of renewable plant oils have created promising new pathways to commercially important specialty chemicals like methyl 9-decenoate and other unsaturated hydrocarbons. Further processing of such compounds with olefin metathesis leads to precious materials for the polymer industry: e.g., as illustrated below, self-metathesis of methyl 9-decenoate furnishes dimethyl 9-octadecenedioate. The price of production, largely driven by cost of the ruthenium metathesis catalyst needed for efficient conversion, remains a critical factor limiting application of these catalysts in production of bulk chemicals.

 

 

4. Reducing manufacturing costs

Industrial Validation: A large specialty chemicals partner wanted to reduce manufacturing costs for a product using a new, more efficient process that incorporated a RCM step. Internal efforts, due to the high dilution required and unacceptably high catalyst loadings, led to unsatisfactory results as the catalyst cost for a production run was projected to be higher than the market price for the final product…

 

5. Developement of an alternative pathways

Industrial Validation: Alternative pathways towards a troublesome small heterocyclic molecule were investigated by Apeiron partner. One of the most promising synthetic routs entailed a three-step process with RCM representing the ultimate reaction in the sequence. Customer’s internal efforts failed to deliver the target molecule in the olefin metathesis-based pathway…

6. Optimization of CM depolymerization reaction

Industrial Validation: A commodity chemicals manufacturer was seeking a feasible process to obtain polymer materials. Despite narrow profit margins Apeiron successfully applied olefin metathesis in the bulk chemistry process…

Development of catalysts tailored for your individual purposes

1. New heterogeneous catalysts supported on SBA-15

Challenge: In many R&D and commercial applications, heavy metal contamination of reaction products is an important concern. Residual ruthenium and ruthenium complexes may catalyze side reactions or adversely impact yields of the subsequent synthetic steps. For example, in the pharmaceutical industry, regulations require that the ruthenium contamination in active pharmaceutical ingredients must not exceed 10 ppm. It is common to observe ruthenium contamination greater than 2500 ppm following an olefin metathesis reaction.

2. Polymerization catalysts soluble in DCPD monomer

Challenge: Polydicyclopentadiene, poly(DCPD), a polyolefinic, cross-linked, thermoset material exhibits outstanding thermal stability, mechanical strength, fracture toughness, and dielectric characteristics. Thanks to these properties poly(DCPD) has become a very attractive polymer for numerous applications and remains one of the most ubiquitous ROMP materials in industrial uses.

The most effective catalysts for DCPD polymerization should exhibit optimal ROMP kinetics and should allow facile handling of the monomer/catalyst formulation. Limitations of currently used ruthenium catalyst relate to the difficult initiation control and poor solubility in neat monomer (requires solvents for solubilization). Both aspects can compromise the physical properties of the resulting polymer.

 

Supportive technologies

Flow reactor

Tube in Tube

Apeiron’s patent pending tube-in-tube reactor design was successfully applied in homo- and heterogeneous olefin metathesis reactions under continuous flow mode. Our reactor efficiently removed ethylene under vacuum conditions thereby significantly improving the outcome of metathesis reactions.

Advantages

  • Efficient and continuous removal of ethylene
  • No scale-up effects
  • High mixing rates
  • Efficient temperature control
  • Marginal concentration gradients

Reference:

  1. US 2014/0288342A1
  2. K. Skowerski, S. J. Czarnocki, P. Knapkiewicz “Tube-In-Tube Reactor as a Useful Tool for Homo- and Heterogeneous Olefin Metathesis under Continuous Flow Mode” ChemSusChem, 7 , (2), 536 – 542 (2014). More

Scavengers

SnatchCat

SnatchCat is a metal scavenger which enables simple and efficient ruthenium and palladium removal.

Advantages

  • Only 2 – 4 eq required
  • Scavenging time 30 minutes
  • Excellent solubility in broad range of solvents
  • High efficiency (usually below 10ppm of Ru or Pd)
  • Reasonable price

Reference:

  1. PCT/IB2014/062564

Supportive technologies

Flow reactor

Tube in Tube

Apeiron’s patent pending tube-in-tube reactor design was successfully applied in homo- and heterogeneous olefin metathesis reactions under continuous flow mode. Our reactor efficiently removed ethylene under vacuum conditions thereby significantly improving the outcome of metathesis reactions.

Advantages

  • Efficient and continuous removal of ethylene
  • No scale-up effects
  • High mixing rates
  • Efficient temperature control
  • Marginal concentration gradients

Reference:

  1. US 2014/0288342A1
  2. K. Skowerski, S. J. Czarnocki, P. Knapkiewicz “Tube-In-Tube Reactor as a Useful Tool for Homo- and Heterogeneous Olefin Metathesis under Continuous Flow Mode” ChemSusChem, 7 , (2), 536 – 542 (2014). More

Scavengers

SnatchCat

SnatchCat is a metal scavenger which enables simple and efficient ruthenium and palladium removal.

Advantages

  • Only 2 – 4 eq required
  • Scavenging time 30 minutes
  • Excellent solubility in broad range of solvents
  • High efficiency (usually below 10ppm of Ru or Pd)
  • Reasonable price

Reference:

  1. PCT/IB2014/062564