Raw Materials: Choice and SourcingProf. Attilio CitterioDipartimento CMIC “Giulio Natta”http://iscamap.chem.polimi.it/citterio/dottorato/

PhD IN INDUSTRIAL CHEMISTRY AND CHEMICAL ENGINEERING (CII)

Attilio Citterio

2Raw Materials and Market

• It is imperative to select the correct raw materials when new synthetic routes need to be designed to produce target products.

• For example, the synthetic route selection for new fine chemicals may evolve in the development process, when the early stages of a synthetic route can be changed without changing the quality or impurity profile of the final drug substance.

• But raw material choice can influence not only the synthetic route but the whole development process.

• The researcher working on development and scale up needs to have a wide knowledge of the fine chemicals market so that he knows not only what available but also what can be made available cheaply.

• Often the only reason a chemical is not available in bulk is lack of demand and not difficulty of synthesis.

Attilio Citterio

3Raw Materials and Market

Whilst it is very easy for the lab chemist to track down sources of laboratory chemicals either through the well-known catalogues or through computer search facilities such as Aldrich or other databases,* it is comparatively difficult to identify the bulk and usually primary sources of even simple fine chemicals, used as raw materials.

It is important for development researcher and engineer to discover the primary source of raw materials since,

• A cheaper price can usually be obtained by disintermediation

but more importantly,

* http://depth-first.com/articles/2011/10/12/sixty-four-free-chemistry-databases/

Attilio Citterio

4Raw Materials and Market

• The quality of raw material will be typical of that used in the future in bulk manufacture and processes are best developed as easily as possible using this grade of material, rather than a “purified” grade sold by a catalogue company.

• Take full advantage of free samples of up to 1 kg which may be available for testing purposes, and detailed analytical and QC information which can often be obtained from the primary source.

The following are compendia which may assist in the process of sourcing. The disadvantage of many of these compendia are that they take so long to produce that the data is inaccurate by the time they go to press. Companies change their product range annually and it is difficult for the compendia to be kept up-to-date

Attilio Citterio

5Compendia for Raw Materials

1. Directory of Chemical Products, published by SRI International

2. Directory of World Chemical Producers, published by Chemical Information Services Ltd, Oceanside, New York, 2007.

3. Some compendia with on line searching facility

• Chemical Sources USA, Directories Publishing Company Florida.

• Chemical Industry Directory, Benn, UK

• Chemcyclopedia, ed. A F Plant, American Chemical Society, Washington.

Attilio Citterio

6How is Sourcing Information Acquired?

• A Chemical Development Department should ideally maintain files of the listings of as many companies as possible.

• Some companies not only produce excellent glossy brochures, butalso interesting reviews on how their products can be applied inindustry. These brochures can be obtained through magazines suchas Chemical and Engineering News, Specialty Chemicals,Performance chemicals.

• Attend exhibitions such as ChemSpec, Dechema, etc. where mostfine chemical companies now exhibit and have lots of especiallyproduced information. This is a good place to make contacts whichmay be useful in the future re sourcing.

• Control access to it to ensure that it is kept in reasonable order andthat files do not go missing.

Attilio Citterio

7How is Sourcing Information Acquired?

• Accessing information which is probably hazard organized, in alphabetical order of company, rather than on the basis of chemical compounds. I have yet to find a satisfactory answer to this. Placing all information on computer records would be time consuming, but very beneficial.

• Some companies only list products which are currently in production. They may have processes developed in the past to make lots of compounds which are not listed, owing to lack of demand. or may have developed processes which have not yet been tested on plant. (Conversely, many companies place products on their list when only lab quantities have been made). Only when enquiries from a customer is received is the expensive development work carried out.

Attilio Citterio

8How is Sourcing Information Acquired?

• However, fine chemical companies are on the look-out for new business and are keen to develop processes to key raw materials if required. But one needs to know who to approach. A thorough knowledge of the fine chemical market is required.

• A further alternative if stuck for a source is to use an agent/trader who usually has a fund of knowledge on where to obtain raw materials, particularly outside Europe, or to use companies such as Interchem and Chemical Exchange Directory, who may charge for their services.

• Of course, at the end of the day, one may still draw a blank. If a synthetic route looks promising based on a raw material which is only available in lab quantities, then there are three alternatives.

Attilio Citterio

9Databases Available at No Cost

Some databases are available free of charge. They give the bibliographic description (with the abstract) of the papers abstracted into these databases. They are available via the Internet. http://www.refdoc.fr/Noticeresultat

Examples INIST (CNRS France)Search made with the terms: palm oilLubrication properties of trimethylolpropane esters based on palm oil and palm kernel oils.European journal of lipid science and technology 2004, vol. 106, pp. 52-60Department of Chemical Environmental Engineering, Faculty of Engineering,University Putra Malaysia, Advanced Oleochemical Technology Center, …Yunus Robiah, Fakhru’l-Razi, Tianlyeool Iyuke, Perez JosephAbstract: E due to the global drive towards biodegradable products, trimethylolpropane[2-ethyl-2-(hydroxymethyl)-1,3-propanedial](TMP) esters based on palm kernels oil ...

Attilio Citterio

10http://www.refdoc.fr/Noticeresultat

Attilio Citterio

11Refdoc.fr Results

Attilio Citterio

12Another Free Database: MEDLINE and Related Data

Attilio Citterio

13Medline (suite)

Attilio Citterio

14The Journal Editors

Many journal editors developed databases available to the public.These databases allow to search the journals edited and to reach the

articles present. Example from ELSEVIEROne of the hits obtained with the words palm oil

Attilio Citterio

15ScienceDirect

http://www.info.sciencedirect.com/

Attilio Citterio

16ScienceDirect

Attilio Citterio

Where to Find these Free Access Journals ?

https://scholar.google.it/ o https://www.google.it/

Attilio Citterio

18Where to Find these Free Access Journals ?

http://www.doaj.org/

Attilio Citterio

19Where to Find these Free Access Journals ?

http://isdm.univ-tln.fr/isdm.html

Attilio Citterio

20Data Science Journal (CODATA Journal)

http://www.jstage.jst.go.jp/browse/dsj

Attilio Citterio

21Chemical Abstracts, one of the best database in the World

Covers Chemistry and related domains (biochemistry, physical chemistry, patents, dissertation, symposium in this field,

CA SEARCH®: CHEMICAL ABSTRACTS®ONTAP® CA SEARCH®: CHEMICAL ABSTRACTS®(FILE 204)Last Loaded on Web: Wednesday, October 01, 2003Chemical Abstracts, one of the best database in the WorldLast Update To Bluesheet: January 23, 200310File DescriptionThe CA SEARCH®: Chemical Abstracts® database includes over 17 million citations to the worldwide literature ofchemistry and its applications from 1967 forward. CA SEARCH corresponds to the bibliographic information andcomplete indexing found in the print Chemical Abstracts® published by CAS® (Chemical Abstracts Service). Thecontrolled vocabulary CA General Subject Index Headings, related general subject terminology from the CA IndexGuide, and CAS® Registry Numbers, each with its modifying phrase are included. Chemical substances are representedby CAS® Registry Numbers, unique numbers assigned to each specific chemical compound: corresponding substanceinformation may be searched in the DIALOG chemical substance files such as CHEMSEARCHTM (File 398). Allrecords from the 8th Collective Index (CI) period forward are contained in File 399; Files 308-314 contain records fromthe individual CI periods as indicated in the File Data.Searches conducted via Dialog®Web Guided Search give customers the option to order the abstracts from CAS®, viaremote links, integrated in the Dialog® search results.

Attilio Citterio

22Chemical Abstracts

Subject CoverageCoverage includes a broad spectrum of chemical information that includes both the basic and appliedchemical sciences. Included are studies of elementary subatomic particles, elements, compounds,and other substances, and their occurrence, composition, structure, preparation, properties, reactions,detection, and determination. The following principal areas of chemical applications and technologies ofchemical substances are included:• Analytical and Physical Chemistry• Applied Chemistry• Biochemistry and Biology• Chemical EngineeringChemical Abstracts• Environmental Chemistry• Macromolecular Chemistry• Organic and Inorganic Chemistry• Pharmaceuticals• Properties and Reactions• Radiation Chemistry• Toxicology

At Politecnico di Milano is active the “SCIFINDER”

suite for any research on published papers,It is directly linked to Chemical Abstract.

Attilio Citterio

23ISI Web of Knowledge, ISI Web of Science

Attilio Citterio

24Books on “Strategy in Organic Synthesis”

1. E. J. Corey, X-M Cheng, The Logic of Organic Synthesis, Wiley, NY, 1989.2.. S. Hanessian, Total Synthesis of Natural Products: The ‘Chiron’ Approach (Pergamon Press,

London, 1983). S. Hanessian, S. Giroux, B.L. Merner, “Design and Strategy in Organic Synthesis: From the Chiron Approach to Catalysis” Wiley-VCH; 2013.

3. Organic Synthesis, Ed. J Fuhrlop and G. Penzin. VCH, Weinheirn, 1987.4. S. Warren: Organic Synthesis: The Disconnection Approach, 2^ Ed. Wiley, 2009.5. Paul Wyatt, Stuart Warren, Workbook of Organic Synthesis: Strategy and Control, Wiley,

2008.6. P. Pollack, Fine Chemicals: The Industry and the Business, Wiley, 2007. C.S. Rao The

Chemistry of Process Development in Fine Chemical and Pharmaceutical Industry 20087. S. Lee, G. Robinson, Process Development: Fine Chemicals from Grams to Kilograms,

Oxford, 1995.8. K. C. Nicolaou, J. S. Chen, “Classics in Total Synthesis III: Further Targets, Strategies,

Methods” Wiley-VCH; 2011.9. P. G. M. Wuts et al. “Greene's Protective Groups in Organic Synthesis” 5th Ed. Wiley, 2014.