Institute of Chemical Research of Catalonia

New method to produce trifluoromethyl copper reagents useful in trifluoromethylation reactions from fluoroform

Posted by Institute of Chemical Research of CataloniaResponsive · Patents for licensing · Spain

Summary of the technology

The trifluoromethyl copper derivative useful in trifluoromethylation reactions is prepared at room temperature from readily available and cheap reagents and in high yield, i.e. without the formation of side-products associated to the fast decomposition of the trifluoromethyl anion, that usually forms in processes involving the deprotonation of fluoroform. This is the first method to date for deprotonation-free, direct cupration of fluoroform, a longly sought after reaction.

Description of the technology

Use of fluoroform as CF3 source in trifluoromethylation reactions We have developed a method to produce trifluoromethyl copper reagents useful in trifluoromethylation reactions from fluoroform, a readily available and cheap reagent. The CF3 group is found in many drugs and agrochemicals, hence the importance of finding a sustainable process for its introduction. We are interested in licensing the method and joint development of the technology.

Specifications

Trifluoromethyl copper (I) compounds that are particularly useful in various trifluoromethylation reactions of organic molecules are conventionally made using costly CF3 sources. Fluoroform, CF3H, is an ideal source of CF3 because it is inexpensive, readily available in large industrial quantities, non-toxic, and not an ozone depleter. However, the few known methods to prepare trifluoromethyl copper (I) compounds from fluoroform are all not only multistep and low-yielding, but also require low temperatures (-10 - -50 ºC) to minimize the extremely facile decomposition of the highly unstable trifluoromethyl anion that is generated in the first, CF3H deprotonation step. Our technology does not involve deprotonation of CF3H. Instead, the CuCF3 reagents are formed via direct cupration that is not mediated by the unstable trifluoromethyl anion and/or difluorocarbene. As a result, our CuCF3 synthesis proceeds cleanly at room temperature while avoiding the formation of side-products. The trifluoromethyl copper reagents are obtained in high yield of up to >90% and can be used directly in various reactions, including aromatic trifluoromethylation. Treatment of a copper(I) source with 2 equivalents of an alkali metal alkoxide results in the formation of highly reactive dialkoxycuprates that directly metalate fluoroform to give CuCF3 compounds in one step. These CuCF3 reagents can then be used in various reactions with electrophiles to give trifluoromethylated products, including trifluoromethylated aromatic and heterocyclic derivatives.

Main advantages of its use

  • Clean production of trifluromethylcopper reagent
  • Environmentally friendly process (fluoroform, which is consumed in the process is a potent greenhouse gas, obtained as a by-product in the preparation of chlorodifluoroethane)
  • Inexpensive and abundant trifluoromethyl source
  • Low-cost reagents
  • Possible stabilization of the trifluoromethyl copper compound
  • Process works at room temperature and atmospheric pressure
  • Scalable process

Applications

  • Chemical compounds bearing a trifluoromethyl group (CF3) are widely used in the production of various pharmaceuticals and agrochemicals as well as specialty materials, polymers, composites, building blocks, and intermediates for various needs
  • Preparation of advanced chemical intermediates, polymer chemistry, pharmaceutical companies, agrochemical companies

Intellectual property status

Granted Patent
EP2678302
Europe

Granted Patent
US20140235866
USA

Related keywords

  • Composite materials
  • Fine Chemicals, Dyes and Inks
  • Plastics, Polymers
  • Agro chemicals
  • Special chemicals, intermediates
  • Pharmaceuticals/fine chemicals
  • Fibre-reinforced (plastic) composites
  • Commodity chemicals and polymers
  • Speciality/performance chemicals
  • pharmaceutical
  • trifluoromethylation
  • fluoroform
  • agrochemical

About Institute of Chemical Research of Catalonia

Technology Transfer Office from Spain

The Institute of Chemical Research of Catalonia represents one of the very first fruits of the new scientific policy of the government of Catalonia (Spain) aimed at creating new research centres in strategic areas. ICIQ, in particular, has been created with the ambition of becoming a reference for chemistry in the European Research Space.

Our society faces important challenges in the XXI century, among which health and environmental concerns are of outmost importance. Chemistry will play an essential role in both of these challenges. To succeed, our increasingly knowledge-based economy will require a solid and strong chemical industry; currently 150.000 jobs in Catalonia (and more than 2 million in the EU) directly arise from the chemical industry. In order for this industry to be successful in the future, it must take a sustainable approach based on the rational use of feed-stocks and raw materials. For this, fundamental chemical research needs to be funded and novel approaches into transforming matter must be developed.

We at ICIQ consider that catalysis is the key activity for sustainable chemistry. Catalytic processes can minimize raw materials and energy consumption, and can lead to the selective formation of target products with minimal generation of wastes. In line with this consideration, we have taken catalysis as one of our main research topics.

Complementary to our research focus, attention has been paid to the development of a simple and efficient organizational model for ICIQ, able to overcome known difficulties normally associated with larger and more traditional research institutions. The Institute of Chemical Research of Catalonia aims at bridging the gap between academic research and industry, focusing its research on catalytic chemical processes for applications in health, energy and sustainability.

At ICIQ, we consider that patents are highly efficient, safe and solid tools to provide protection from competitors. This is why we file patents for our in-house developed-technologies: to give our co-development projects with industry a strong starting IP position. As a research centre our goal is always to co-develop our technology adapting it to the industrial partner’s specific needs and ultimately transfer the technology to this company, with a flexible licensing strategy adapted to each case.

Send your request

By clicking "Send your request" you are signing up and accepting our Terms of Service and Privacy policy

Technology Offers on Innoget are directly posted and managed by its members as well as evaluation of requests for information. Innoget is the trusted open innovation and science network aimed at directly connect industry needs with professionals online.