Author Archives: Dominique Hebrault

Continuous Flow Chemistry Publications

I recently helped some colleagues and customers with literature references on the use of real time in situ mid-IR spectroscopy (ATR-FTIR) applied to flow chemistry. Considering all the reaction condition improvements (yields, purity, simplicity) described in these papers, I thought I would share the list with the chemical community. The papers are from a variety of academic research groups including Klavs Jensen at MIT (USA), Steven Ley and Ian Baxendale at the University of Cambridge (UK), Paul Knochel in Munich (Germany) and Floris Rutjes in the Netherlands. There are also a few papers from Industry, e.g. Merck (USA), and Pfizer (USA). Continue reading

R&D in the Chemical Industry – Houston

My colleagues and I organized an R&D in the Chemical Industry event in Houston, Texas.  The one day event was for R&D chemists and engineers involved in chemical and petrochemical process research, optimization, and scale-up.

The conference was held at the Westin Galleria Houston on August 20. It featured six presenters who shared their experience and best practices. Around 40 participants attended from companies that included:

  • Albemarle
  • Baker Hughes
  • Celanese
  • Dow Chemical
  • ExxonMobil
  • Momentive
  • Nalco
  • Shell

After an introduction to innovative technologies for in situ measurements of process parameters by METTLER TOLEDO technical experts (Anjan Pandey, Dom Hebrault), Allen Beard, Process Development Advisor at Albemarle gave the first talk on the practical aspects of reaction calorimetry for process safety and scale-up. Allen began with an introduction of best process safety practices at Albemarle, followed by two case studies. The first one, a Gatterman-Koch formylation reaction, described the use of reaction calorimetry for in-depth safety and kinetic understanding. Although RC1e calorimetry is well known for process safety investigations, I was especially impressed with Allen’s use of thermal conversion for the full kinetic modeling of the multi-phase Gatterman-Koch reaction (CO gas and multiple liquid phases). The Runge-Kutta numerical method was used in Mathcad. The dependency of rate contant as a function of temperature for the various equilibria was eventually determined. The second case study, butene oligomerization for jet fuel production, offered the audience a fascinating tale of process safety criticality as a function of reaction conditions. He used the method from Professor Francis Stoessel, Head of Chemical Process Safety Consulting at the Swiss Institute for the Promotion of Safety and Security in Basel, that is described in Stoessel’s 2008 book “Thermal Safety of Chemical Processes” (ISBN-10: 3527317120). Allen described the benefits of using iC Safety software to model the process criticality index.

Kaytlin Henry, Senior Engineer at Dow Chemical, gave us a compelling account for the use of mid-IR and Raman real time spectroscopy for the kinetic modeling of polymerization reactions, e.g. ethylene, propylene, and butylene oxides. The use of combined automated reactor technologies with real time monitoring provided a full kinetic model, eventually yielding shorter development time, and increased process productivity. I especially liked the part when Kaytlin described the use of closed loop control where in situ measurement directed the instantaneous relative addition rate of each individual monomer in order to control molecular weight distribution according to the Mayo-Lewis equation (instantaneous copolymer composition determination). This led to the remarkable ability to predict and control in real time the physical properties of the final copolymer product. Although this kind of control was straightforward to set up by Kaytlin at the liter scale, she mentioned it’s unfortunate that the same level of automated control is still extremely challenging to implement at plant scale.

Chemical R&D Houston

Kaytlin Henry of Dow Chemical

I had the pleasure to invite and introduce Jerry Salan, the third speaker, CEO and founder of NALAS Engineering, whom I have known for almost 10 years. Jerry briefly described the research services his company provides in process development and scale-up of fine and specialty chemicals, and then offered two case studies. The first one dealt with the scale-up and safety aspect a hydroboration – hydrolysis sequence. The goal was a scalable  process for a 3000-liter run.  Initial thermodynamic data collected on an RC1e reaction calorimeter provided enough process information to develop a heat transfer model for each step. I was especially interested in the resulting optimum non-linear dosing profile. Although unusual, it makes perfect sense to add slowly at the beginning when the reaction is fast and faster at the end when the reaction tends to slow down, in order to maintain a safe, productive, and cost-efficient process. I’ll definitely keep this in mind for future process development studies. The second study focused on one of Jerry’s fortes since his years developing explosives with the US Navy: 50-liter scale-up synthesis of a dinitropyrazine derivative. A high end modeling study including solubility, heat transfer, and rate, was made from initial process data collected on an RC1e equipped with a ReactIR probe. DSC and CRC90 data were also fed in to the model. AKTS software provided the kinetic model that enabled a decomposition reaction scenario to be predicted (Time to Maximum Rate TMR and TD24). As a result, facing a process deemed too hazardous to be run in a batch mode, Jerry and his colleagues proved that an alternative continuous nitration process would ensure a safe, reliable, and practical 50-liter scale-up.

Finally, John Tolsma from RES Group , a company that provides process modeling services to resolve engineering issues for energy, chemical, and pharmaceutical companies, gave us a great demonstration of his company’s capabilities on an ethylene-vinyl alcohol copolymer example. Faced with a process providing high molecular gel by-products yielding costly reaction shutdowns for cleaning, the RES team developed a comprehensive model based on RC1e reaction calorimeter, Raman, and infrared data including chemical kinetics and gel formation mechanism. It provided reaction rate prediction, including off-specs by-products, leading to a better understanding of the copolymer molecular structure and enhanced physical properties for the final material. A continuous process with two cascade stirred tank reactors (CSTR) was designed as a result that would offer the benefit of minimized off-specs product formation, and better cost-efficiency.

I would like to thank the participants and the speakers who made the conference a success. Two conference breaks and a networking reception gave ample opportunities for peer to peer interaction and some fun! For those of you who have not yet had a chance to participate in these one-day, no charge events, we are hosting two other events: La Jolla, CA on October 10 and Cambridge, MA on October 30.  Unlike the event in Houston, where most participants were from the chemical and petrochemical industries, the events in La Jolla and Cambridge are focused on fine chemicals and pharmaceuticals and biotechnology.  We will also host several events in 2014.

I hope you’ll get a chance to join us next time. We look forward to meeting you!

Continuous Flow Chemistry & Crystallization Development Symposium

In pharmaceutical development, the drive for better drug product quality, process reliability, efficiency and safety have become key factors in driving chemists and engineers to seek alternative methodologies. Continuous flow reactor technologies significantly expand the range and scope of possible chemistries, and allow for rapid testing, optimization, and scaling of chemical sequences. This is reflected in the dramatic increase in the variety and depth of published chemistry over the last few years. Continue reading

第42届全美有机化学学术报告会 (NOCS)

我在六月五日至九日参加了在新泽西州的Princeton 大学召开的第42届全美有机化学学术报告会 (NOCS) 。本届学术报告会由美国化学学会(ACS) 的有机化学部门与Princeton 大学的化学系共同组织,邀请了十三位报告人士。不少报告是针对新发现化学、生物学及学术研究 – 全都同时强调了有机化学的新进展

到会的人员大约有350名化学研究生与本科生、助教、教授、以及新发现和工艺过程化学师。据我估计,三分之二的参会者来自学术界,其余三分之一似乎来自制药或生物科技工业。约有10%的参会者来自美国之外的国家。

我期待着参加将于2013年在西雅图的华盛顿大学召开的第43届全美有机化学学术报告会 (NOCS)

NESACS’s Bench to Plant Symposium

NESACS SymposiumUpon returning to the Boston area after a number of years away, I was very much looking forward to attending The Northeastern Section of the American Chemical Society (NESACS)’s Advances in Chemical Sciences “Bench to Plant” Symposium for the first time.  Held in Cambridge on October 22, about 100 scientists from the local area gathered for the one day Symposium focusing on Process R&D Chemistry, Organic Synthesis, and New Synthetic Methodology.

Some highlights of the top-notch presentations included:

Continue reading

使用实时分析和工艺过程自动化来走向绿色

秋季里,我在于波士顿举办的第三届制药与精细化学品工业的绿色工艺加工国际学术报告会上作了一个报告。会议之后,化学经理欧洲杂志(CHEManager Europe Magazine)的主编联系了我,希望我根据我的报告:“使用实时分析和工艺过程自动化来走向绿色”写一篇文章。因为我对可持续发展充满激情,我立即接受了这一邀请。该文已发表在化学经理欧洲杂志的一月份期刊上,只需快捷的注册便可进行阅读。

请自由地张贴您的见解或问题。我会高兴地回应及提供更多细节。

Going Green Using Real-Time Analytics & Process Automation

In the fall, I presented a paper at the 3rd International Symposium on Green Processing in the Pharmaceutical & Fine Chemical Industries in Boston.  Continue reading