Reagents for pharmaceutical synthesis

Transcription

1 eagents for pharmaceutical synthesis

2 2 Welcome to AkzoNobel AkzoNobel is proud to be one of the world s leading industrial companies. In fact, we are the largest global paints and coatings company. As a major producer of specialty chemicals we supply industries worldwide with quality ingredients for life s essentials. We think about the future, but act in the present. We re passionate about introducing new ideas and developing sustainable answers for our customers. We have operations in more than 80 countries, and employ around 55,000 people, who are committed to excellence and delivering Tomorrow's Answers Today. ur Functional Chemicals business makes organic peroxides, metal alkyls, organometallic specialties and polymer additives. We supply essential products used in polymer production and processing, as well as in chemical synthesis of small molecule drugs. We have a long history in the manufacture and supply of metal alkyls and organic peroxides. Today, we're a global leader with a broad range of metal alkyls, including aluminum, magnesium, boron and zinc alkyls. And we're the world's top producer of organic peroxides. We can help your production of intermediates and active pharmaceutical ingredients with our finest chemical reagents and specialty chemicals. We also offer custom-manufactured organometallic compounds and specialty chemicals. AkzoNobel: Looking beyond horizons At AkzoNobel we look beyond horizons. We believe that what is good for you today is not necessarily good enough for you tomorrow. We are committed to the success of our customers. We offer you the technological answers you need.

3 3 The finest chemical reagents In pharmaceutical synthesis, our products are especially useful in reduction, addition, alkylation, and deprotonation, where our reagents facilitate a wide range of asymmetric steps. Some of our products are presently used in the production of the world's leading blockbuster drugs. We invite you to visit our website at for complete product listings. ur expertise and facilities find growing use in the synthesis of specialty chemicals that are used in the pharmaceutical and fine chemical industries. We want to be your preferred supplier, producing custom specific products through arrangements protected by confidentiality agreements. What do you need? From gram-scale to multiple-metric-ton level, we're happy to meet with you and discuss you target molecule. AkzoNobel s key commercial chemical reagents and specialty chemicals for pharmaceutical synthesis rganometallic eagents CAS no. Acronym Chemical name Formula DIBAL- Diisobutylaluminum hydride (i-c 4 9 Al DIBAL-BT Diisobutylaluminum butylated oxytoluene (i-c 4 9 Al(C 6 2 (C 3 )(t-c 4 9 ) TMAL Trimethylaluminum (C 3 ) 3 Al TEAL Triethylaluminum (C 2 5 ) 3 Al DEAC Diethylaluminum chloride (C 2 5 AlCl DEB-M Diethylboron methoxide or Diethylmethoxyborane or Methoxydiethylborane (C 2 5 BC TEB Triethylborane (C 2 5 ) 3 B DEZ Diethylzinc (C 2 5 Zn DMZ Dimethylzinc (C 3 Zn DNBM Di-n-butylmagnesium (n-c 4 9 Mg BEM n-butylethylmagnesium n-c 4 9 MgC TDC Titanocene dichloride or Bis(cyclopentadienyl) titanium (IV) dichloride (C 5 5 TiCl 2 Peroxides and Initiators AIBN 2,2 -Azodi(isobutyronitrile) (C 3 C(CN)N=NC(C 3 CN BP Dibenzoyl peroxide (C 6 5 C CP Cumyl hydroperoxide or Cumene hydroperoxide C 6 5 C(C MCPBA m-chloroperoxybenzoic acid ClC 6 4 C TBP tert-butyl hydroperoxide (C 3 ) 3 C

4 4 Applications of our products in pharmaceutical synthesis DIBAL- Diisobutylaluminum hydride ydride eduction ydride reduction, including epoxide to alcohol, enone to allylic alcohol, carboxylic acid to primary alcohol, lactone to cyclic alcohol, amide to aldehyde, amide to amine, and nitrile to aldehyde. For example: DIBAL- DIBAL U. S. Pat e n t 5, 0 8 6, ( ) T e t r a h e d r o n L e t t., 3, ( ) DIBAL-BT Diisobutylaluminum butylated oxytoluene Asymmetric eduction DIBAL-BT J. r g. C h e m., 4 4, ( ) 95% yield 92%ee DEZ Diethylzinc Cyclopropanation (Simmons-Smith) Asymmetric Addition DEZ, C 2 I 2 2 Et DEZ Ti(iPr) 4, ligand up to 99% ee M a r c h s A d va n c e d r g a n i c C h e m i s t ry, 5 t h E d. W i l e y, N e w Y o r k ( ), p U. S. Pat e n t 6, 6 6 0, B 2 ( ) J. A m. C h e m. S o c., 7 0, ( ) TMAL Trimethylaluminum Alkylation Weinreb Amidation 3 CCI TMAL 3 CC 3 TMAL N 1 (C 2 3 AI-N C 3 CC 3 2 C 2 C(C 3 (C 3 AI-N 1 2 C 2 C(C 3 ) N 1 2 J. r g. C h e m., 3 5, ( ) J. C h e m. S o c. C h e m. C o m m., ( ) J. r g. C h e m., 6 2, ( ) r g. S y n., ( )

5 5 DEB-M Diethylboron methoxide or Diethylmethoxyborane or Methoxydiethylborane Asymmetric eduction DEB-M, NaB T e t r a h e d r o n L e t t., 2 8, ( ) U. S. Pat e n t 5, 1 8 9, ( ) TEB Triethylborane Asymmetric eduction TEB, NaB U. S. Pat e n t 4, 6 8 1, ( ) U. S. Pat e n t 5, 2 7 3, ( ) Asymmetric eduction (via lithium triethylborohydride) TF Li + Et 3 B LiEt 3 B LiEt 3 B, TF 2 99% endo J. r g. C h e m., 4 5, 1 ( ) Free adical Mediated Synthesis I + -C=C 2 TEB/ % I C h e m. e v., 1 0 1, ( )

6 6 TDC Titanocene dichloride or Bis(cyclopentadienyl) titanium (IV) dichloride Tebbe lefination C 2 TDC Me 3 Al J. A m. C h e m. S o c., 1 0 0, ( ) DNBM Deprotonation MgBu 2 Li C 2 Bu 2 Mg BuLi i) C 2 or (Me C ii) + Et 2 T, 4 hr =, 70% =Me, 74% A n g e w. C h e m. I n t. E d., 4 6, 2 ( ) DEAC Diethylaluminum chloride Diels Alder eaction + DEAC S e e f o r e x a m p l e J. A m. C h e m. S o c., 1 1 2, ( ) AIBN 2,2 -Azodi(isobutyronitrile) adical Initiator NBS AIBN Br M a r c h s A d va n c e d r g a n i c C h e m i s t ry, 5 t h E d., W i l e y, N e w Y o r k ( ), p

7 7 CP Cumyl hydroperoxide or Cumene hydroperoxide Asymmetric xidation 1. Ti(-iPr) 4 (S,S)-diethyl tartrate S 1 S (ipr NEt CP > 95% ee T e t r a h e d r o n A s y m m e t ry, 1 1, ( ) MCPBA m-chloroperoxybenzoic acid Baeyer-Villiger xidation Epoxidation MCPBA NaC 3 1 C C 3 MCPBA 1 C C J. r g. C h e m., 6 3, ( ) M a r c h s A d va n c e d r g a n i c C h e m i s t ry, 5 t h E d., W i l e y, N e w Y o r k ( ), p xidation S 1 MCPBA S 1 T e t r a h e d r o n A s y m m e t ry, 1 1, ( ) TBP tert-butyl hydroperoxide Asymmetric Epoxidation (Sharpless) TBP Ti(-iPr) 4 95% ee J. A m. C h e m. S o c., 1 0 2, ( )

8 8 Logistics and technical support AkzoNobel operates manufacturing facilities for organometallic reagents and organic peroxides in the Americas, Europe, and Asia. ur versatile facilities and flexible production schedules enable us to supply your favorite products from a few grams to multiple tons, and anything in between. ur global distribution network allows us to deliver the products to you anywhere in the world. Security of Supply We at AkzoNobel always place safety as our top priority in customer service. ur Safety esearch laboratory in Deventer, the Netherlands, conducts routine safety tests on our products and develops protocols for your safe handling. ur safety programs combine classroom learning and live demonstrations with on-site consulting, to assist you in receiving and using our products. We also offer design and maintenance services at your sites to support your handling and storage of hazardous materials. All production sites are IS 9001 and IS certified in order to ensure the highest product quality and strictest compliance with environmental regulations. Additionally, our sites in the Americas have achieved C certification. egional headquarters Manufacturing sites &D sites

9 9 AkzoNobel is consistently ranked as one of the Chemicals industry leaders on the Dow Jones Sustainability World Indexes (DJSI), showing that we take our obligations seriously - to the planet, to our customers, to our own people. We believe the only way to grow is by developing sustainable, innovative solutions that benefit our customers. And we're constantly looking for ways to reduce our impact on the environment. We're committed to esponsible Care, Product Stewardship and EAC. For product inquiry and ordering information, please contact your AkzoNobel account manager or regional AkzoNobel sales office. Americas for Mexico Akzo Nobel Chemicals, S.A. de C.V. Av. Morelos No. 49 Col. Tecamachalco Los eyes La Paz Estado de Mexico C.P Mexico T F E polymerchemicals.mx@akzonobel.com for Brazil Akzo Nobel Ltda. odavia Akzo Nobel no. 707 Portão A Planta C Bairro São oque da Chave Itupeva - São Paulo Brazil T F E polymerchemicals-sa@akzonobel.com for other countries AkzoNobel Functional Chemicals 525 West Van Buren Street Chicago, IL US T (US only) T F E polymerchemicals.na@akzonobel.com Europe, Middle East and Africa for France, Italy, Spain and Portugal Akzo Nobel Chemicals, S.A. Autovia de Castelldefels, km El Prat de Llobregat Barcelona Spain T F E polymerchemicals.es@akzonobel.com for ussia and CIS AkzoNobel Akzo Nobel N.V., epresentative ffice Smolnaya Str., 24D, Commercial Tower Meridian Moscow ussia T F E info.moscow@akzonobel.com for Middle East AkzoNobel P.. Box 290 Al Quouz Industrial Area Sheikh Zayed wy. Dubai United Arab Emirates T F E polymerchemicals.nl@akzonobel.com for other countries AkzoNobel Functional Chemicals Stationsstraat M Amersfoort P.. Box AE Amersfoort The Netherlands T F E polymerchemicals.nl@akzonobel.com Asia Pacific Akzo Nobel (Asia) Co., Ltd. The Exchange, 5th floor 299 Tong en oad Shanghai P.. China T F E polymerchemicals.ap@akzonobel.com for India Akzo Nobel Chemicals (India) Ltd. Tellus Building, 2nd floor 209/1B/1A ange ills Pune Maharashtra India T /85/86 F E sales.ancil@akzonobel.com Additional information Product Data Sheets (PDS) and Material Safety Data Sheets (MSDS) are available at

10 All information concerning these products and/or all suggestions for handling and use contained herein are offered in good faith and believed to be reliable. AkzoNobel Functional Chemicals and its affiliates, however, make no warranty as to the accuracy and/or sufficiency of such information and/or suggestions, as to the products merchantability or fitness for any particular purpose, or that any suggested use will not infringe any patent. Nothing contained herein shall be construed as granting or extending any license under any patent. Buyer must determine for himself, by preliminary tests or otherwise, the suitability of these products for his purposes. The information contained herein supersedes all previously issued bulletins on the subject matter covered. The user may forward, distribute and/ or photocopy this document only if unaltered and complete, including all of its headers and footers, and should refrain from any unauthorized use. You may not copy this document to a website. AkzoNobel is the largest global paints and coatings company and a major producer of specialty chemicals. We supply industries and consumers worldwide with innovative products and are passionate about developing sustainable answers for our customers. ur portfolio includes well known brands such as Magala, Perkadox, Trigonox, Sikkens and Eka. eadquartered in Amsterdam, the Netherlands, we are a Global Fortune 500 company and are consistently ranked as one of the leaders on the Dow Jones Sustainability Indexes. With operations in more than 80 countries, our 55,000 people around the world are committed to exellence and delivering Tomorrow's Answers Today AkzoNobel Functional Chemicals, all rights reserved "Tomorrow s Answers Today" is a trademark of Akzo Nobel N.V _290611