Post on 15-Aug-2021
transcript
Aldrich
VOLUME 11 NUMBER 3 2011
Synthetic Reagents
Catalysis
Organometallics
Building Blocks
Specialty Synthesis
Stable Isotopes
Stockroom Reagents
Labware Notes
Potassium carbobenzyloxycyanamide: an efficient reagent for amine guanylation
Order your 2012–2014 Aldrich® Handbook.
The new Aldrich Handbook contains the widest selection of chemistry and materials science products and is your resource for chemical structures, literature references, and extensive chemical and physical data. Our complimentary catalog includes new and innovative reagents and building blocks, plus a focused line of Labware products to support your chemistry needs.
The Aldrich Handbook’s portfolio supports the research community with:
• More than 40,000 research chemicals
• Over 4,000 new products
• 10,000 chemical structures
• 8,500 updated literature citations
• Extensive chemical and physical data
For reliable, high-quality chemicals you can trust, add your free copy of the Aldrich Handbook to your laboratory by visiting:
Aldrich.com/newcatalog
76873
76873_ALD_catalog_ad_Acta-Chemfiles_8.25x10.indt 2 7/29/2011 11:24:42 AM
Introduction 3
Aldrich
Haydn Boehm, Ph. D.Global Marketing Manager: Chemical Synthesis
haydn.boehm@sial.com
Dear Fellow Chemists,
Welcome to the third installment of Aldrich ChemFiles for 2011, our complimentary quarterly innovation newsletter written by experts from Aldrich Chemistry Product Management and R&D.
Our aim is to keep you informed of the new Aldrich Chemistry products that facilitate the latest research methodologies and trends, and allow you to access key starting materials and reagents more efficiently.
As well as introducing all the latest innovations across all of our product lines, in 2011 each edition of Aldrich ChemFiles is themed to a product line. Aldrich ChemFiles Vol. 11, No. 3 will focus on our Synthetic Reagents product line. In this issue’s lead article, Troy Ryba, Product Manager, highlights our new ChiroSolv® EnantioPrep™ Kits which define scalable, optimized chiral resolution methods, to deliver pure enantiomers within a matter of days. Our “Synthetic Reagents” cover molecule is potassium carbobenzyloxycyanamide, which is an efficient reagent for amine guanylation.
Aldrich ChemFiles Vol. 11, No. 3 will also introduce the latest innovations across all of our product lines including new chiral catalysts and applications (Catalysis), chiral crotylsilanes and EZ-CrotylMixes (Organometallics), halogenated pyridines and aldehydes (Building Blocks), and new ionic liquids (Speciality Synthesis). I would also like to draw attention to Aldrich’s new normality and molarity calculators (acid and base molarity/normality, mass molarity, and solution dilution) which have been updated on our website at Aldrich.com/calculator and are now available as iPhone® and iPad® applications.
We hope that Aldrich ChemFiles will enable you to expand your research toolbox and advance your chemistry more effectively by implementing the latest innovative synthetic strategies.
Kind regards,
Dr. Haydn Boehm Global Marketing Manager: Chemical Synthesis
Sigma-Aldrich Corporation6000 N. Teutonia Ave.Milwaukee, WI 53209 USA
Editorial TeamHaydn Boehm, Ph.D.Wesley SmithDean LlanasSharbil J. Firsan, Ph.D.Weimin Qian
Production TeamCynthia SkaggsVincent ClarkChris LeinTom BeckermannChristian HagmannDenise de Voogd
Chemistry TeamLeslie Patterson, Ph.D.Aaron Thornton, Ph.D.Daniel Weibel, Ph.D.Josephine Nakhla, Ph.D.Ronaldo Mariz, Ph.D.Pietro Butti, Ph.D.Mark Redlich, Ph.D.Troy Ryba, Ph.D.Todd Halkoski Paula FreemantleMike Willis
Aldrich ChemFiles SubscriptionsTo request your FREE subscription to Aldrich ChemFiles visit Aldrich.com/chemfiles or contact your local Sigma-Aldrich office (see back cover).
Aldrich ChemFiles OnlineAldrich ChemFiles is also available in PDF format at Aldrich.com/chemfiles.
Aldrich Chemistry ProductsAldrich brand products are sold through Sigma-Aldrich, Inc.Sigma-Aldrich, Inc. warrants that its products conform to the information contained in this and other Sigma-Aldrich publications. Purchaser must determine the suitability of the product for its particular use. See reverse side of invoice or packing slip for addi-tional terms and conditions of sale. All prices are subject to change without notice.
To Place Orders or Contact Customer/ Technical ServicesContact your local Sigma-Aldrich office (see back cover).
Aldrich ChemFiles (ISSN 1933–9658) is a publication of Aldrich Chemical Co., Inc. Aldrich is a member of the Sigma-Aldrich Group. © 2011 Sigma-Aldrich Co. LLC.
Volume 11, Number 3
Table of ContentsSynthetic Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Organometallics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Building Blocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Specialty Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Stable Isotopes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Stockroom Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Labware Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
4
Synthetic ReagentsTroy Ryba, Ph.D.Product Managertroy.ryba@sial.com
Potassium Carbobenzyloxycyanamide: An Efficient Reagent for Amine Guanylation*
N CNK
O
O
carbobenzyloxycyanamide potassium salt
N CNK
Cbzor
L499994
Figure 1. Structure of Potassium carbobenzyloxycyanamide.
The reaction of amines with an activated carbodiimide represents a powerful method for the preparation of guanidines. A simple and efficient one-pot method for the synthesis of mono-protected guanidines is presented in Scheme 1. Treatment of this cyanamide with trimethylsilyl chloride generates a reactive N-silylcarbodiimide capable of guanylating a variety of amines. Typically the reaction is complete in 15 minutes for primary and secondary aliphatic amines at room temperature. Anilines are also reactive but require a little more time. This method is operationally simple, high yielding at room temperature, and adequate purification is usually achieved through aqueous acid / base work up which can remove excess amine or cyanamide, respectively.
NCN
K
TMSCl1.1 equiv.
1.1 equiv. MeCN, rt.
NCbz
N NH2
R1
R2CbzN
CbzN
SiMe3
NH
R2R1
NCbz
N NH2
R1
R2
NH
N NH2
R1
R2H2 (1 atm)
Pd/C MeOH
Eq. 1
Eq. 2
Scheme 1: Applications of potassium benzyloxycarbonylcyanamide
amine product yield (%)
NH2Me NH
Me NH2
NCbz
85%
time
NH
NH2
NCbz
N NH2
NCbzMe
Me
Me Me
N NH2
NCbz
N NH2
NCbz
O
NH
NH2
NCbz
NH
NH2
NCbzMeO
NH
NH2
NCbz
F
N NH2
NCbz15 min
15 min
15 min
15 min
15 min
88%
91%
NH2
NH
NH
NH
NCbz
NH2
NH
NH2
ONH
8 h 83%
16 h 73%
16 h
63%
NH
NH
Me
Me
Me
Me
NH2
MeO
NH2
NH2F
N NH2
NCbz
16 h
68%NH
MeMe
92%
90%
73%1 h
NH
NH2
NCbz
NH2
O2NO2N
91%
-- N.R
15 min
Figure 2. Examples of amine guanidinylation with potassium carbobenzyloxy-cyanamide.
References: Looper, R. E.; Haussener, T. J.; Mack, J. B.C; 2011, submitted.* Article provided courtesy of Prof. Ryan E. Looper, University of Utah.
NH3C
CH3
BH3
R H
O
R R
O
PEMB, AcOH
NH2,R rt
PEMB, AcOH
NH2,R 50 o C
R H
N
R R
N
R
H R
H
ExamplesAldehyde and Amine Conditions Product
% Yield in MeOH(% Yield Neat)
PhNH2
CHOPEMB, AcOH
MeOH, 25 oC
NH
Ph 72(80)
CHO
Pr2NH
PEMB, AcOH
MeOH, 25 oC PrN
Pr 0(96)
C4H9 CHO
PhNH2
PEMB
MeOH, 25 oC C4H9
HN
Ph92
(94)
O
PhNH2
PEMB, AcOH
MeOH, 25 oC
HN
Ph 92(93)
H3C C3H7
O
PhNH2
PEMB, AcOH
MeOH, 50 oC H3C C3H7
HNPh
74(94)
For more examples and experimental detailBurkhardt, E. R.; Coleridge, B. M. Tetrahedron Lett. 2008, 49, 5152.
5-Ethyl-2-methylpyridine borane (PEMB)725080
Select Substrate Scope
PEMB is a liquid Pyridine Borane Complex useful for reductive amination chemistry.
Advantageous Properties of PEMB:• Excellent for reductive aminations
• Mild reducing agent for imines and oximes
• Reaction with protic solvents is very slow
• Soluble in aromatic hydrocarbons, alcohols andether solvents
• Can be used solvent-free for reductive aminations
• Chemically effi cient: two-of-three hydrides are utilized
Add Aldrich to your research program. Aldrich.com/pemb
Contact Aldrich Chemistry for research quantities under 500 grams.
For quantities over 500 grams, contact BASF.
When you need a stable liquid Reductive Amination Reagent.
76684
76684_PEMB_Ad_right_facing.indd a 7/29/2011 2:41:58 PM
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
6
ChiroSolv® EnantioPrep™ Kits Deliver Pure Enantiomers*
In 2007, Sigma-Aldrich began offering ChiroSolv Screening kits as useful tools to identify the optimal chiral resolution conditions for racemates. Very recently, Chirosolve, Inc. introduced ChiroSolv EnantioPrep Kits that provide scalable, optimized chiral resolution methods and that deliver pure enantiomers within a matter of days.
EnantioPrep is designed to obviate the obstacles analytical chemists face during the elaborate process of diastereomeric crystallization. It offers a well-established method to identify a comprehensive set of chiral separation options, deliver pure enantiomers, and define a scalable chiral separation. What sets EnantioPrep apart from other method development tools is the inclusion of ChiroSolv Screening Kits that allow for 384 unique reagent combinations to identify optimal separation conditions. It is an extremely time and resource efficient approach to chiral resolution that allows analytical chemists to skip over the hard part of finding an optimal or scalable method to achieving an enantiopure product.
Key Features:
•Four Screening Kits offer exhaustive screening to identify best separation conditions
•Purify Kits allow quick recovery of racemate
•Self-contained design of the product allows streamlined and consistent process for method development and to get pure enantiomer
•Very little amount of racemate is needed (0.5–4 g)
•Results within 2 weeks; up to 90% of theoretical enantiomer yield
Key Benefits:
•Fast delivery of isolated enantiomer at a target purity and yield needing minimal amount of racemate
•Cost-efficient method development through iterative crystallization accelerates the lead optimization and preclinical studies
•Consistent results provide solid basis for developing complete separation strategy
•Value-creating foundation builds differentiated patent estate
•Works with any racemate (acid, base, alcohol, aldehyde, ketone, amino acid, racemate with multiple chiral centers)
How do ChiroSolv Solutions Work?ChiroSolv EnantioPrep Kits use the method of diastereomeric crystal-lization, a process that chemically separates enantiomers in a racemic mixture by complexation with an enantiopure acid or base, resulting in a mixture of diastereomeric salts. These salts have different chemical and physical properties, which allow their separation. This well established technology competes favorably with newer techniques such as asymmet-ric synthesis, biocatalysis, enzyme resolution, kinetic resolution, or chiral chromatography.
One major advantage of diastereomeric crystallization is that the proce-dure scales up easily for manufacturing purposes. Today around 65% of chiral products are made using this technique.
Examples:
•Paroxetine is a selective serotonin reuptake inhibitor developed by Novo Nordisk’s subsidiary, Ferrosan, and licensed to GlaxoSmithKline. It is sold as the hydrochloride salt under the name Paxil® for the treatment of depression, anxiety, and obsessive–compulsive disorder. It is prepared by resolution using (–)-di-p-toluoyl-l-tartaric acid.
•Setraline is an antidepressant that inhibits the uptake of serotonin in the central nervous system and is sold by Pfizer under the name Zoloft®. Diastereomeric crystallization of the racemate by (R)-mandelic acid is used in its preparation.
•2-Amino-5-methoxytetralin is an intermediate in the synthesis of N-0923 (Nagase & Co., Ltd., Japan), a potent dopamine D2 receptor agonist, effective against Parkinson’s disease (currently in clinical trial). This intermediate is resolved by diastereomeric salt formation with (S)-mandelic acid. The undesired isomer is then racemized and reused in an iterative process.
•In the synthesis of AG-7404 (Pfizer), a key intermediate was resolved by (–)-norephedrine. The final compound was obtained by the combination of diastereomeric and enzymatic resolution.
How to Use ChiroSolv EnantioPrep Kits
Screen racemate against 384separation conditions
Recover racemate usingrecovery solution
Check purityand yield
Heat, Cool
Repeat until targetenantiomeric purity
is achieved
Purify racemate using thebest separation condition
Extract puri�edenantiomer ready
for testing
The experiment involves Three phases of work:
1. Screening: Racemate is screened against 384 different combinations of resolving agents and solvents. When the combination of the racemate, resolving agent, and solvent is heated together, diastereomeric salt of one enantiomer preferentially crystallizes out after cooling. The best combination of the reagent and solvent that offers the highest yield and enantiomeric enrichment for the target enantiomer is chosen to do further enrichment.
2. Recovery: After collecting all the material used during the screening process, which includes the racemate, resolving agents, and the solvents, this phase will treat it with our “recovery solution” that will separate out the racemate from the resolving agents in the form of two
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
7Synthetic Reagents
liquid layers. Using separatory funnel, these layers will be separated and the racemate (typically > 90%) will be recovered from the bottom layer
3. Purification: The goal of this phase is to identify how many recrystallization steps are required to get the enantiomeric purity needed. The end result should be a smaller quantity of enriched enantiomer (maximum yield: about 35% of the total racemate given).
EnantioPrep allows scientists to:
•Quickly screen a racemate against a comprehensive list of 384 resolving agent/solvent combination to identify all possible resolution conditions
•Recover the used racemate and proceed to purify it until target purity is achieved
•Define a step-by-step resolution method that can be scaled up to kilo quantities
This purification solution can be used for racemic acids, bases, alcohols, amino acids, aldehydes, and ketones.
EnantioPrep includes a set of four Acid or Base Series Screening Kits, Recovery Solution for acid or base racemate that recovers up to 90% racemate used during screening; and a self-contained Purification Package that allows incremental purification of enantiomer through simple steps.
Example Kit.
Each individual screening kit is in a disposable, ready-to-use, 96-vial, high-throughput format that allows the entire analysis to be performed inside the kit without removing any vials. The kit is made of polypropylene material that can withstand extreme temperatures (–20 to 120 °C), allowing the entire kit to be placed in a hot-water or ice bath without damage. The set of four screening kits offers unique 384 combinations of resolving agent/solvent combinations, so that a full set of separation conditions can be identified early on to help the rest of the research. Resolving agents are chosen with manufacturing use in mind; they are relatively inexpensive and recoverable in high yield after the resolution is complete. The high-throughput format allows scientists to explore the separation conditions in parallel and get results within 24 hours, which may otherwise take over two months.
When the Recovery Solution is added to the diastereomeric salts of the racemate and the resolving agents, it breaks the diastereomeric salt into neutral racemate that goes in the organic layer; while the resolving agents stay in the aqueous layer. Separating these two layers and removing the residual solvents from the organic layer returns the original racemate.
The Purification Package includes a filter funnel with vacuum adapter, enantiomer and filtrate collection bottles, spare filters, and pH paper. After recovering the racemate from Screening Kits (using the Recovery Solution), the resolving agent and solvent combination associated with best separation condition is selected to get incrementally purified salt of the target enantiomer until the required purity is achieved. Finally the enantiomer is extracted from the diastereomeric salt. In our experience, if you use 5 g of racemate during purification, depending on the number of recrystallization steps needed, you can get up to 2 g of pure enantiomer. The entire purification typically requires up to eight hours of hands-on work giving results within one week.
Types of KitsAcidThe acid screening kits include a distinct group of chirally pure acids and is used to resolve racemic bases and amino acids (some pre-processing is required for amino acids). Examples of resolving agents in the acid kits are:
•(–)-Camphoric acid
•(+)- and (–)-Camphorsulphonic acid
•(+)- and (–)-Dibenzoyltartaric acid
•(–)-Malic acid
•(+)- and (–)-Mandelic acid
•(+)-Lactic acid
•(+)- and (–)-Tartaric acid
BaseThe base screening kits include a distinct group of chirally pure bases or amines, and is used to resolve racemic acids, alcohols, aldehydes, and ketones (some pre-processing is required for the latter three). Examples of resolving agents in the base kits are:
•(–)-2-Aminobutanol
•(–)-Brucine
•(–)-Cinchonidine
•(+)-Cinchonine
•(+)-Dehydroabietylamine
•(+)- and (–)-Methylbenzylamine
•(+)-Quinidine
•(–)-Quinine
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
8
Case Studies with ChiroSolv® EnantioPrep™ SolutionChiroSolv EnantioPrep kits were used for two sample racemates:
•N-Benzyl-1-(4-methylphenyl)propane-2-amine (racemate had 70% S and 30% R isomer). Goal was to get over 90% purity for R isomer. This racemate was resolved by di-tolyltartaric (+) acid in 100% IPA.
Case Study Results Racemate Desired isomer purity Starting material Amount recovered # of recrystallization Amount of pure enantiomer
N-Benzyl-1-(4-methylphenyl)propane-2-amine R isomer, >90% purity 1.046 g 0.996 g (95%) 4 280 mg
N-Benzyl-1-(4-benzylphenyl)propane-2-amine R isomer, >90% purity 1.931 g 1.738 g (90%) 3 700 mg
After two recrystallizations, we were able to obtain 30% S and 70% R. Additional two recrystallizations yielded > 90% enrichment in R. The yield was over 90% of theoretical value.
•N-Benzyl-1-(4-benzylphenyl)propane-2-amine (racemate had 50% S and 50% R). Goal was to get over 90% purity of the R isomer. This racemate was resolved by S-acetylmandelic acid (+) in 90% IPA. After two recrystallizations, we were able to obtain 80% R and 20% S, with yield over 80% of theoretical value.
Representative Scope
DBU, Et3N 3HF, or Et3N 2HF* promoters:
R OH
XtalFluor-E or -M
+ promoter *substrates products
R H
O
R R
O
R OH
O
RS
O
CH3
R F
R H
R R
R F
O
RS F
F F
F F
O
OHRO
RO
RORO O
FRO
RO
RORO
XtalFluor reagents are crystalline dialkylaminodifluoro sulfinium tetrafluoroborate salts. They are useful for the deoxo fluorinationof hydroxyl and carbonyl moieties when used in conjunction with a promoter.*
Advantages of XtalFluor salts
Aldrich XtalFluor Reagents
H3C
H3CN=SF2 BF4 – –O N=SF2 BF4
+ +
719439 719447
XtalFluor-E® XtalFluor-M®
XtalFluor-E and XtalFluor-M are registered trademarks of OmegaChem Inc.
Multi-kilogram quantities available through Manchester Organics
Looking for a Safer Fluorinating Reagent?
Aldrich.com/xtalfl uors
References: (1) Beaulieu, F. et al. Org. Lett. 2009, 11, 5050. (2) L’Heureux, A. et al. J. Org. Chem. 2010, 75, 3401.
• Air-stable solids
• Enhanced thermal stability over DAST and other structurally similar deoxofl uorination reagents
• Broad substrate scope
• Predictable and high chemoselectivity
sh4078
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
9Synthetic Reagents
Facile and Rapid Chiral Resolution with ChiroSolv® EnantioPrep™ KitsThere are four Acid Series kits and four Base Series kits, available individually, or as the complete acid or base set. Each individual kit is in a ready-to-use, 96-vial, high-throughput format that allows the entire analysis to be performed inside the kit without removing any vials. The kit is made of polypropylene material that can withstand extreme temperatures (–20 to 120 °C), allowing the entire kit to be placed in an oven or ice bath without damage.
The kits can be supplied in two different formats, either as kits for solid racemates or kits for liquid racemates. The kits for liquid racemates provide calibrated quantities of a unique resolving agent and solvent combination in each vial. The racemate can then simply be added to start the screening process. The kits for solid racemates allow the researcher to dissolve the racemate into a volatile solvent and then dispense the resultant solution into each vial containing a resolving agent. The volatile solvent is evaporated and the prepared screening solvents are then dispensed from a separate plate into each vial.
Resolving agents are chosen with manufacturing use in mind; they are relatively inexpensive and recoverable in high yield after the resolution is complete. Using all four kits in an acid or base series, 384 resolving agent–solvent combinations can be explored for a single racemate. The high-throughput format allows scientists to identify within 24 hours the optimum resolution process which might otherwise take over two months.
ACID BASE12 solvents
384 combinations
8 Res
olving
Agents
Series 1
Series 2
Series 3
Series 4
Series 1
Series 2
Series 3
Series 4
96 vials
96 vials
96 vials
96 vials
96 vials
96 vials
96 vials
96 vials
0
5
10
15
20
25
16 32 48 96 144 192 240 288 336 384
No. of Resolving Agents
Manual Screening Screening with ChiroSolv Kits
No.
of D
ays
Requ
ired
Time Savings Using ChiroSolv Kits
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
10
Recap: How to Use ChiroSolv® Kits1. Choose the right kit type (Acid Series 1, 2, 3, 4 or Base Series 1, 2, 3, 4)
depending on the identity of the racemate.2. If the racemate is an alcohol, amino acid, aldehyde or ketone, you may
need to pre-process the racemate.3. Add 0.03 mmol of your racemate to each of the 96 vials. Depending on
the availability of the dispensing autostation and the racemate. type (liquid or powder), you may need to remove the seal on the vials. Note the seal is pierceable to accommodate direct injection of racemate by liquid dispensers.
4. In an oven or water bath, heat the rack along with its vials to 80 °C (optimal temperature for most of these experiments) or until the mixture becomes homogeneous.
5. Allow the kit to cool to ambient temperature. If required, further cool it to 4 °C or 0 °C to observe crystallization. Vials with crystals are considered positive results and should be examined further.
6. Often, more vials with positive results can be obtained using standard crystal initiation techniques. Vials with no crystals even after this effort are considered negative results.
7. Separate out the positive test results and note their alphanumeric identification.
8. Liberate the enantiomers from their diastereomeric salts and analyze by optical rotation. Typically, only one or two vials will show maximal optical purity.
Features•Eight types of ready-to-use disposable kits providing a total of 768
resolving agent–solvent combinations.
•Very little amount of racemate required (less than 3 mmol per kit).
•Concentrations of the resolving agents are calibrated to give accurate results and optimal crystallization.
•Pierceable seal allows easy racemate dispensing; vials held together by a plastic ring so that vials can be picked up and inspected together for crystal formation.
•Easy to follow, step-by-step instructions and results charts.
•Conveniently designed for easy robotic manipulations.
•Kits and vials have unique identification (barcode or alphanumeric) for cross-referencing.
•Long shelf life at room temperature (2 years).
Each rack has a unique barcode.
Each vial contains a unique combination of
resolving agent/solvent— 8 types of kits give 768 such
combinations.
Pierceable septa or foil seal for easy
robotic manipulation.
Plastic sleeve holds the vials together even when they are out of
the rack.
Each vial has a unique alphanumeric identification.
Rack, vials, and septa are chemically inert and can withstand –20 °C to 120 °C.
Extra septum mat provided in kits for
solid racemates.
Product Information for Liquid RacematesProduct No. Product Name/Description681431 ChiroSolv Resolving Kit, Acid Series 1681423 ChiroSolv Resolving Kit, Acid Series 2681415 ChiroSolv Resolving Kit, Acid Series 3699217 ChiroSolv Resolving Kit, Acid Series 4700363 ChiroSolv Resolving Kit, Complete Acid Series681407 ChiroSolv Resolving Kit, Base Series 1681393 ChiroSolv Resolving Kit, Base Series 2681377 ChiroSolv Resolving Kit, Base Series 3699241 ChiroSolv Resolving Kit, Base Series 4700371 ChiroSolv Resolving Kit, Complete Base Series
Product Information for Solid RacematesProduct No. Product Name/Description698881 ChiroSolv Resolving Kit, Acid Series 1699527 ChiroSolv Resolving Kit, Acid Series 2698873 ChiroSolv Resolving Kit, Acid Series 3699225 ChiroSolv Resolving Kit, Acid Series 4700398 ChiroSolv Resolving Kit, Complete Acid Series699233 ChiroSolv Resolving Kit, Base Series 1698938 ChiroSolv Resolving Kit, Base Series 2698946 ChiroSolv Resolving Kit, Base Series 3698954 ChiroSolv Resolving Kit, Base Series 4700401 ChiroSolv Resolving Kit, Complete Base Series
For more information, please visit Aldrich.com/chirosolv
Synthetic Reagents
Kits: A1, A2, A3, A4 or B1, B2, B3, B4
Analyze selected vials with crystals for specific rotation
Select vials with crystals & note their alphanumeric
identification
Unknown Racemate
Cool mixture 4 °C to 0 °C Yes
No
Cool mixture to ambient temp.
Heat mixture to 80–100 °C
Ready to Use Disposable Kit
Need a MolarMatic™ Measuring Cylindersfor your Acid solutions?
Aldrich MolarMatic Measuring Cylinder
Our MolarMatic graduated measuring cylinder allows you to add concentrated acid to the desired molarity line. Simply pour the measured acid into one liter of water, and your 1 M, 2 M, or 3 M solution is prepared.
• No calculations
• No struggling for the correct cylinder
Convenient Dual-Scale Graduated Cylinder• Class A, 350-mL cylinders
• Graduated in 5.0-mL increments; calibrated "to deliver"
• 1 to 3 Molar scale on opposite side
• Eliminates repetitive molar calculations and potential errors
• Set contains one of each cylinder in plastic storage case
Acid Type Cat. No.
Acetic acid Z683728
Hydrochloric acid Z683736
Nitric acid Z683744
Sulfuric acid Z683752
Set of four Z683760
Save time. Add Aldrich.Aldrich.com/molarmatic
75634
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
12
CatalysisRonaldo Mariz, Ph.D.Product Managerronaldo.mariz@sial.com
ZACA Catalyst: Enabling Flexible Asymmetric Synthesis Through Carboalumination of Terminal AlkenesSince the seminal work of Nobel laureate Ei-ichi Negishi using ZACA catalyst (719072),1 the zirconium catalyzed asymmetric carboalumination reaction (ZACA reaction) of terminal alkenes has allowed highly flex-ible design for the syntheses of chiral organic compounds. For instance, proper treatment of the carboaluminated intermediate from inexpensive allyl alcohol gives rise to versatile building blocks through a one-pot procedure which can undergo further Pd-catalyzed functionalization (Scheme 1).2
H3O+
Me
HO IMe
TBSO I
TBSCl, DMA
(-)-ZACA catalyst - (R)-product(+)-ZACA catalyst - (S)-product
* *80%82%
Me
TBSO* CH2
Me
TBSO*
CO2Me
MeMe
TBSO*
TMS
Me
TBSO* Me
O
[Pd] [Pd]
[Pd] [Pd]
HOCH2
1) Me3Al (2.5 eq)2) 719072 (5 mol%) MAO (1 eq)
Me
Me2AlO AlMe2
I2(2.5 eq) Me
Me2AlO I
Scheme 1: One-pot procedure for the synthesis of versatile protected and unprotected 3-iodo-2-methyl-1-propanol via ZACA reaction.
Probing its flexibility, Negishi’s group has demonstrated that when followed by vinylation the ZACA reaction can be sequentially used to construct multiple stereogenic centers. This methodology furnishes an elegant entry to deoxypolypropionate, residues present in many natural products with interesting medicinal properties and biological activity such as doliculide (Scheme 2).2,3
CH2
Me
TBSO
1) (i) (+)-ZACA; (ii) Pd-cat.vinylation2) (i) (+)-ZACA; (ii) O2
Me
TBSO
MeMe
OH
52%1) NaH, BnBr2) TBAF3) Dess-Martin oxid.4) EtO2CCH=PPh3
77% (4 steps)
Me MeMe
OBnEtO2C
steps
(R) (S) (S)
MeMe
O
O
OHMe
Me
Me
MeN
O
NH
OHI
HO
doliculide
(S)
(S)
(R)
Scheme 2: Sequential ZACA reaction to construct multiple stereogenic centers.
References: (1) (a) Kondakov, D. Y.; Negishi, E. J. Am. Chem. Soc. 1995, 117, 10771. (b) Kondakov, D. Y.; Negishi, E. J. Am. Chem. Soc. 1996, 118, 1577. (2) Liang, B.; Novak, T.; Tan, Z.; Negishi, E. J. Am. Chem. Soc. 2006, 128, 2770. (3) Negishi, E. ARKIVOC 2011, viii, 34.
H3C
H3CCH3
CH3
CH3H3C
Cl Zr Cl(-)-ZACA catalyst
719072
For a list of zirconium catalysts available from Aldrich Chemistry, visit Aldrich.com/zirconium
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
13Catalysis
p-Tol-BINASO: A Highly Active and Selective Ligand for Rhodium-Catalyzed Asymmetric Conjugated Addition The rhodium-catalyzed asymmetric 1,4-addition reaction has emerged as a powerful tool for the formation of C-C bonds over the last decade.1 Recent reports by the group of Prof. Dorta at the University of Zürich showed excellent results by using a C2-symmetric bis-sulfoxide ligand based on the binaphthyl moiety. High activity and selectivities were en-countered in the addition of boronic acids to α,β-unsaturated cyclic esters and ketones under mild conditions when applying rhodium p-Tol-BINASO complex (Scheme 1).2
1.1 eq. ArB(OH)2
[(p-Tol-BINASO)]RhCl]2(1.5 mol% Rh)
KOH (50 mol%)toluene/H2O (10/1)
40 °C
+X
O
X
O
Ar*
2.0 h98% yield, 90% ee
CH3
1.0 h60% yield, 99% ee
1.5 h93% yield, 99% ee
1.0 h94% yield, 97% ee
1.5 h93% yield, 99% ee
1.0 h91% yield, 97% ee
Ar =F
CH3 CF3
Cl F
1.0 h55% yield, 97% ee
OMe
1.0 h97% yield, 96% ee
1.5 h86% yield, 98% ee
1.5 h90% yield, 98% ee
Ar =
CH3 Cl
F
0.5 h99% yield, 96% ee
O
Ph
O
Ph
3.0 h98% yield, 66% ee
O
O
Ph
1.0 h98% yield, 91% ee
O
2-naphthyl
1.0 h, 98% yield, 94% ee (1:1 cis:trans)
H3C
1.0 h92% yield, 99% ee
1.0 h99% yield, 90% ee
1.0 h89% yield, 96% ee
Ar =
1.0 h90% yield, 95% ee
OMe
1.0 h99% yield, 98% ee
O
2-naphthyl
H3C
Scheme 1: Rhodium-catalyzed 1,4-addition of boronic acids to α,β-unsaturated esters and ketones using p-Tol-BINASO.
While an excess of boronic acid was required for most systems used for this transformation, the ligand enabled coupling of ortho, meta, and para substituted aryl boronic acids using only 1.1 equivalents of the nucleo-phile. In addition, only 1.5 mol% of rhodium is needed instead of the 3 mol% normally required to preform the reaction in short time at a mild 40 °C, which is in contrast to the higher temperatures frequently applied.
References: (1) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829. (2) (a) Mariz, R.; Luan, X.; Gatti, M.; Linden, A.; Dorta, R. J. Am. Chem. Soc. 2008, 130, 2172. (b) Burgi, J.; Mariz R.; Gatti, M.; Drinkel, M.; Luan, X.; Blumentritt, S.; Linden, A.; Dorta, R. Angew. Chem. Int. Ed. 2009, 48, 2768. (c) Mariz, R.; Bürgi, J.; Gatti, M.; Drinkel, E.; Luan, X.; Dorta, R. Chimia 2009, 63, 508. (d) Mariz, R.; Poater, A.; Gatti, M.; Drinkel, E.; Burgi, J.; Luan, X.; Blumentritt, S.; Linden, A.; Cavallo L.; Dorta, R. Chem. Eur. J. 2010, 16, 14335.
Aldrich Chemistry is pleased to offer researchers this promising chiral sulfoxide ligand.
S
S
OO
CH3
CH3
(P,S,S)-p-Tol-BINASO
726443
S
S
OO
CH3
CH3
(M,S,S)-p-Tol-BINASO
726443726435 726443
For a list of chiral catalysts and ligands available from Aldrich Chemistry, visit Aldrich.com/asymmetriccatalysis
Takasago Ligands and Complexes: Excellence in Catalysis Technology Now at Reduced PricesThe research team at Takasago International Corporation has developed excellence in catalysis through continuous improvements for over a quarter century. This work has translated into cutting edge catalysis technology for many chemical transformations with special emphasis on asymmetric synthesis (Scheme 1).
R1 R2
O
R1 R2
OH
R1 R2
NH2or
R1 R3
R2
R1 R3
R2
R2
R1 NR3
R3
R2
R1X
O
n
CO2t-Bu X
O
n
CO2t-BuF
X = O, NH, NR
R1 H
O
R1
OH
O
H
CN
R1 R2
O
R1 R2
OH
R3
R3 = vinyl, aryl
NR1
R2
R3
XR3
HN
R1 R2
+
Reduction of ketones toalcohols or amines
Arylation and vinylationof ketones
Reduction of Alkenes Cyanomethylation
Fluorination Conversion of allylamine to aldehydes
or
B(OH)2Ar
or
ArR3
Buchwald-Hartwig Amination and Suzuki cross-coupling
Scheme 1: Examples of reactions performed by Takasago ligands and complexes.
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
14
Aldrich Chemistry is pleased to offer the over 70 Takasago ligands and complexes at reduced prices.
PPh2PPh2
693065
PPh2PPh2
O
O
O
O
692395
CH3
P(t-Bu)2
711179
PPh2PPh2
692387
OMePPh2
693537
CH3
PCy2
702943
P(t-Bu)2
CH3
693383
PCy2
CH3
702951
OP PPh PhPh Ph
692344
O
O
O
O
P
PRu
NH2
H2N
R R
R RPh
Ph
Cl
ClR =
CH3
CH3
693200
For a complete list of Takasago ligands and complexes, visit Aldrich.com/takasagocatalysts
New Palladium Catalysts and Precursors for Cross-coupling Reactions
N N
Pd
N
Cl
Cl Cl
CH3H3C
CH3
H3C
H3C CH3
H3C
CH3
732117
P
PdNH2Cl
H3CO
OCH3
t-Bu OCH3
704946
Pd NH2
Cl
Pi-Pr
i-Pr
i-Pr
704954
Pd NH2
Cl
P t-But-Bu
i-Pr
i-Pr
i-Pr
708739
P
PdNH2Cl
O
O
t-Bu OCH3i-Pr
i-Pr
707589
P
Pd
H3CO
OCH3
i-Pr
i-Pr
i-Pr
NH2
Cl
718750
A comprehensive list of palladium catalysts and precursors for cross-coupling reactions is available from Aldrich Chemistry in a useful application guide format, Aldrich.com/pdapplicationguide
Need Chemical Compounds for Your Research?Let us supply the chemicals so you can concentrate on the science!
Aldrich® Custom Packaged Reagents
AldrichCPR provides pre-weighed, application ready building blocks and screening compounds, allowing you to focus on discovery rather than the tedious process of sourcing, procurement, and preparation.
Provide your list of MFCD numbers, CAS numbers, CNC IDs, structures, and/or vendor and product numbers, and Aldrich Chemistry will source, package, and send your chemicals to you.
Aldrich.com/CPRAldrichCPR@sial.com
76758
Continually introducing new and innovative Boronic Acid Surrogates to meet your research needs, our vast line of organotrifluoroborates feature:
•Air and moisture stability
•Less prone to protodeboronation
•Stability to common and harsh reagents, and reaction conditions
From the latest product innovations to the widest selection of solvents on the market, your research will move forward faster when you add trustworthy products, services, and information from Aldrich Chemistry.
Add Aldrich to your research program.
When you need a Trifluoroborate for your cross-coupling.
Aldrich.com/tfb
681342
BF3KBr
662984
BF3K
711144
NH
N
BF3K
729299
BF3KBr S
720747
BF3K
CH3
CH3
720682
BF3K
CH3
H3C
723797
BF3KS
728837
BF3K
NCI
728810
KF3B N
N OCH3
710075
FF
F
S
B
NH+
-
710083
CH3
BF3
NH
N
723916
BF3K
CH3H2C
76253
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
16
OrganometallicsAaron Thornton, Ph.D.Product Manageraaron.thornton@sial.com
EZ-CrotylMix: A Comprehensive Solution to the Enantioselective Crotylation of AldehydesEnantioselective crotylation reactions have been the focus of an enormous amount of effort within the field of organic synthesis. This reaction’s ability to form C-C bonds, as well as set adjacent stereocenters, has been critical to the construction of numerous complex molecules. The first general approach to this transformation was disclosed by Professor H.C. Brown and co-workers in 1986, in the form of their chiral crotylborane methodology (Scheme 1).
CH3
B CH3
2
CH3
B
2CH3
CH3
B
2CH3
CH3
B
2
CH3
Scheme 1: Brown’s chiral crotylboranes.
Despite the fact that Brown’s methodology has been the method of choice for the past 20 years, significant shortcomings remain. Of particular importance is the inherent diastereofacial bias of certain chiral aldehydes that is often difficult, or even impossible, to overcome. Also, the Brown method is hampered by the use of somewhat impractical synthetic techniques, including the use of harshly basic organometallic species, air and moisture sensitive Lewis acids, and the need for low temperature manipulations.
The group of Professor James Leighton previously developed reagents for the enantioselective crotylation of aldehydes based on the use of their chiral crotylsilanes (Scheme 2).1
NSi
N
H
H
Br
Br
CH3Cl
733180
NSi
N
H
H
Br
Br
CH3Cl
733083
NSi
N
H
H
Br
Br
Cl
CH3
733199
NSi
N
H
H
Br
Br
Cl
CH3
733075
Scheme 2: Leighton’s crotylsilane reagents.
While these reagents have made significant strides in addressing many of the previously mentioned shortcomings of the Brown method, still an overall lack of substrates that undergo productive reaction with these reagents significantly limits their application (Scheme 3).
BnOO
H
733180
CH2Cl2, 0 o CBnO
OH
CH3
BnOOH
CH3
733199
CH2Cl2, 0 o C
82 % yield96 % ee
83 % yield99 % ee
PhCH3
O
H
CH3
O
H
SiOH3CH3C
PhPh 733199
or733180
733199
or733180
No Reaction
Scheme 3: Representative examples of successful and unreactive substrates.
Based on the knowledge that Lewis acids may be used to catalyze the reaction of similar allylboranes with aldehydes by binding to one of the boronate oxygen atoms, the Leighton group hypothesized that a similar strategy may be useful for activating their crotylsilane reagents. Now, with the addition of just 5 mol% Sc(OTf )3, the enantioselective crotylation of previously unreactive aldehydes may now be performed with excellent yield and enantioselectivity (Scheme 4). Importantly, this new method utilizes air-stable crystalline solids that can easily be weighed out and manipulated at room temperature.2
PhCH3
O
H
733075
5 mol% Sc(OTf)3CH2Cl2, 0 oC
PhCH3
OH
CH3
87% yield94% ee
PhCH3
OH
CH3
733083
5 mol% Sc(OTf)3CH2Cl2, 0 oC
87% yield91% ee
Scheme 4: Sc(OTf )3 catalyzed enantioselective aldehyde crotylation.
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
17Organometallics
To further increase the utility of this method, the Leighton group has shown that simply premixing the chiral crotylsilane reagent and Sc(OTf )3 leads to a versatile reagent that simplifies reaction set-up even further. This bench-stable reagent, termed EZ-CrotylMix, can now be used for the enantioselective crotylation of previously unreactive substrates, with the crotylation of α-methylcinnamaldehyde yielding the desired product in 89 % yield with 92 % ee (Scheme 5).
CH3
O
H
SiOH3CH3C
PhPh
CH3
OHSiOH3CH3C
PhPh
CH3
85% yield97% ee
(R,R)-trans EZ-CrotylMix(737674)
CH2Cl2, r.t.
PhCH3
O
H PhCH3
OH
CH3
89% yield92% ee
(S,S)-cis EZ-CrotylMix(737666)
CH2Cl2, r.t.
Scheme 5: EZ-CrotylMix for the enantioselective crotylation of aldehydes.
Aldrich Chemistry has now teamed with Prof. Leighton to make these powerful reagents commercially available. These reagents show a number of advantages over previously developed crotylation products, including:
•Crystalline solids that can be weighed in air on the benchtop
•Provide excellent reactivity and selectivity
•Have a truly broad substrate scope
To learn more about Leighton’s EZ-CrotylMix reagents available from Aldrich Chemistry, visit Aldrich.com/ezcrotylmix
References: (1) Hackman, B. M.; Lombardi, P. J.; Leighton, J. L. Org. Lett. 2004, 23, 4375. (2) Kim, H.; Ho, S.; Leighton, J. L. J. Am. Chem. Soc. 2011, 133, 6517.
Chiral Crotylsilanes and EZ-CrotylMixes from Aldrich
NSi
N
H
H
Br
Br
CH3Cl
733180
NSi
N
H
H
Br
Br
CH3Cl
733083
NSi
N
H
H
Br
Br
Cl
CH3
733199
NSi
N
H
H
Br
Br
Cl
CH3
733075
NSi
N
H
H
Br
Br
CH3Cl
Sc(OTf)3
25 737674
NSi
N
H
H
Br
Br
CH3Cl
Sc(OTf)3
25 737682
NSi
N
H
H
Br
Br
Cl
CH3
Sc(OTf)3
25 737666
NSi
NCH3
Cl
Br
Br
H
H
25
Sc(OTf)3
737658
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
18
Building BlocksMark RedlichProduct Managermark.redlich@sial.com
Halogenated PyridinesPyridines continue to be extremely popular building blocks for synthetic chemists across a number of disciplines. The pyridine moiety is found in a wide range of synthetic targets with applications in catalysis, drug design, molecular recognition, and natural product synthesis. Halogenated pyridines in particular are attractive building blocks for various cross-cou-pling methodologies. Aldrich Chemistry offers these useful halogenated pyridines for your research.
New Halogenated Pyridines
N SH
NO2
724793
N CF3
F
730181
N Br
Cl
725188
N F
NH2
728675
N Br
F
723339
N Br
HO
725072
N F
NH2
720232
N Br
F F
733997
N Br
Br
725196
N NO2
Cl
714585
N NH2F 725064
NBrNH2
O 714526
N
NH2
Cl
725056
N
Br
O OH
714658
N
NH2F
732176
N
ClO2N
Cl 724297
N
BrO2N
Cl 730157
N
FCl
NH2 714631
New Halogenated Pyridines — continued
N
NH2Br
F 722391
N
BrF3C
Cl 728748
N
CH3F
Br 731072
N
BrF3C
F 733237
N
F
Br
OH
O
722448
For a complete list of available halogenated pyridines available from Aldrich Chemistry, visit Aldrich.com/hal-pyr
New Aldehydes
S
Br
O
H
716553
N
S Cl
Cl
H
O 724300
H
O
CH 725021
I
OCH3
H
O
729450
H
O
F
F
Cl 728985
O
H
H3CO
715778
H
O
Cl 715786
Cl
H
O
725722
NN
OCH3
H3C
H
O
732508
NN
Br
H3C
H
O
732494
For a complete list of available aldehydes available from Aldrich Chemistry, visit Aldrich.com/aldehyde
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
19Building Blocks
Other New Building Blocks
• O CH3
OH3C
714984
S
Cl
O
734454
S
Br CN
731315
NN
Br
CH3
CH3
715344
NN
O OCH3
730203
N
N
Cl
HN
732095
N
N
CF3
NH2 709131
N
N
ClH2N
732281
N
N
Cl
H2N 732133
O
N
N
Cl
Cl
Cl
728772
N
N
NH2
Br OCH3
732125
NH
Cl
I 707120
HN
N NH
O
731935
O
OI
732842
O
OICl
732869
O
OIBr
732877
For a comprehensive list of building blocks available from Aldrich Chemistry, visit Aldrich.com/bb
To discover Microreactor Technology & Flow Chemistry
Product Name Product No.
Microreactor Explorer Kit 19979-1KT
Microreactor Explorer Kit
Our all-in-one solution allows you to explore innovative newtechnologies right away at a highly attractive price:
• Improve product profiles, purities, and yields of your products
• Perform scale-independent synthesis from mg to kg in a single day
• Control highly exothermic reactions
• Handle unstable or hazardous materials (even explosives) safely
• Minimize the time frame for process development
Improve safety and cost. Add Aldrich.
Aldrich.com/mrt76072
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
20
Specialty SynthesisPietro Butti, Ph.D.Product Managerpietro.butti@sial.com
Ionic Liquids: A Smart AlternativeEnvironmentally low-impact alternatives, sustainable processes, industrial ecology, and efficiency are some of the topical words which are directing the development of the new generation of technologies and products.1 Therefore, the importance of compounds coming from renewable feed-stock or enabling high levels of recycling is growing exponentially. These compounds are seen as promising materials able to replace compounds produced with fossil fuel sources, hence reducing our global dependence upon them.2
NNR' R'' N
R
R
NR''' R'
R''
R
PR''' R'
R''
Figure 1: Commonly used ionic liquids aprotic cations.
NTf2
PF6
BF4
OTf
CH3COO
NO3 Br
CF3COO
Cl
Water Miscibility
Figure 2: Commonly used ionic liquids aprotic anions.
Ionic liquids have been recognized and developed by scientists from academia and the chemical industry as new green(er) chemicals.3 Even if they are not always the “greenest choice”, 4 ionic liquids, a group of salts that exist as liquids at relatively low temperatures (<373 °K) (Figures 1 and 2), have gained overwhelming interest over the past decades (Chart 1). They offer unique sets of properties, often difficult to achieve with any other compounds. Some of these properties are chemical and thermal stability, non-flammability, and low vapor pressures.5
Publications per Years
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
19901991
19921993
19941995
19961997
19981999
20002001
20022003
20042005
20062007
20082009
2010
Year
Num
ber o
f Pub
icat
ions
Chart 1: Number of SciFinder® hits containing the words “Ionic Liquids” from 1990 to 2010. Red total number of publications, Gray filtered through patent applications.
This class of compounds opens up a variety of opportunities in many dif-ferent applications. For example, chemical processing and fine chemicals synthesis such as the BASIL™ process (Scheme 1).6
N
NR2PCl
EtOH NH
N
Cl-+ +R2POEt
Recycle
Scheme 1: Preparation of alkoxyphenylphosphines (R2POEt) with the BASIL process.6
Another example is the olefin metathesis, published by Grela and co-workers in 2007 (Scheme 2).7
TsNTs
N
H2C CH2CH3 CH3
O
Ru
CH3
H3C
Cl
Cl
NMesMesN
N
PF6
Up to >98% Conversion5 Cycles
5 mol%,
BMIM PF6 (70956)Tol, 3h, 25°C
Scheme 2: Recyclable catalytic system for a model metathesis reaction.7
Ionic liquids are also used in polymer and biopolymer processing as enabling technology to utilize cellulose.1,8 In electrochemical applications and in metal processing9 they offer unprecedented prospects for metal deposition. Furthermore, they can be used in nuclear fuel processing.10 They lead to new opportunities in separation processes, or their tune-able properties can be exploited to prepare engineering fluids or other high-performance materials. Ionic liquids are also used in analytical chemistry11 (Supelco’s GC capillary column SLB-IL series) and biomedical applications.12 These examples highlight just a few of the large number of potential applications in which this class of extraordinary compounds can be used.
Publications per Years
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
21Specialty Synthesis
References: (1) Pinkert, A.; Marsh, K. N.; Pang, S.; Staiger, M. P. Chem. Rev. 2009, 109, 6712–6728. (2) Xie, H.; King, A.; Kilpelainen, I.; Granstrom, M.; Argyropoulos, D. S. Biomac-romolecules, 2007, 8, 3740. (3) Keskin, S.; Kayrak-Talay, D.; Akman, U.; Hortacsu, O. J. of Supercritical Fluids, 2007, 43, 150–180. (4) Jessop, P. G. Green Chem., 2011, article in press DOI: 10.1039/C0GC00797H (5) Zhu, S.; Wu, Y.; Chen, Q.; Yu, Z.; Wang, C.; Jin, S.; Ding, Y.; Wu, G. Green Chem., 2006, 8, 325. (6) Maase, M. Multiphase Homogeneous Catalysis, 2005, 2, 560–566. (7) Rix, D.; Caïjo, F.; Laurent, I.; Gulajski, L.; Grela, K.; Mauduit, M. Chem. Commun., 2007, 3771–3773. (8) Maase, M.; Massonne, K.; Uerdingen, E.; Vagt, U.; ChemFiles, 2006, 6(9), 3 (9) Abbott, A. P.; Frisch, G.; Hartley, J.; Ryder, K. S. Green Chem., 2011, 13, 471–481. (10) Nash, K. L; Lumetta, G. J. Advanced Separation Techniques for Nuclear Fuel Reprocessing and Radioactive Waste Treatment. 2011, 1. (11) Soukup-Hein, R. J.; Warnke, M. M.; Armstrong, D. W. Annual Rev. Anal. Chem., 2009, 2, 145–168. (12) Elliott, G. D.; Kemp, R.; MacFarlane, D. R.; Plechkova, N. V.; Rogers, R. D.; Seddon, K. R. Ionic Liquids: From Knowledge to Application. 2009, 6, 95–105.
For a complete list of ionic liquids, available from Aldrich Chemistry, visit Aldrich.com
N+
H3C CH3
PF6–
713198
N+
H3C CH3
Br–
713171
N+
H3C CH3
BF4–
713163
N+
H3C CH3
SO
ON–F3C S CF3
O
O 713155
CH3N+
H3C
I–
713139
CH3N+
H3C
PF6–
713120
CH3N+
H3C
O SO
OCF3
727725
N+
N
CH3
CH3
CH3
BF4–
713023
N+
N
CH3
CH3
CH3
PF6–
713015
N+
H3CCH3
PF6–
713090
N+
H3CCH3
BF4–
713082
N+
H3C
SO
ON–F3C S CF3
O
OCH3
713074
N
N+CH3
I–
CH3 713031
N
N+CH3
CH3
I–
713066
N
N+CH3
CH3
I–
713058
N
N+
N– SSO
OCF3
O
OF3C
CH3
CH3
711705
SO
ON–F3C S CF3
O
OCH3N+
CH3
CH3
H3C
713007
N+I–
CH3
CH3 713112
N+
CH3
BF4–
713104
N NH3C
H2C
I 727717
N NH3C
H2C
CNCN
N 727709
N NH3C SO
ON–F3C S CF3
O
O
H2C
727695
N NH3CCH3
O
ONH2
727911
N NH3CCH3
OH 728527
O SO
O
FF
FF
N NH3CCH3
727687
N NH3CCH3
O
OCH3
NH2 727903
N NH3CCH3
O
O
HO 726257
NCH3
CH3 CH3
SO ON–
CF3
SCF3
O OH3C
727989
NCH3
H3C
CH3
OCH3
SO ON–
CF3
SCF3
O O
727679
N
N+
N–S
S
OOCF3
OOCF3
CH3
CH3 727954
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
22
Aldrich NMR SolventsChallenge Us… And See Why Our Quality is Unsurpassed!
High quality NMR solvents are essential for satisfying the most rigorous demands of NMR-based research and analyses. At Aldrich, we are pas-sionate about providing this high level of quality to our customers and work continuously to meet these requirements. We offer the widest range of NMR solvents with the highest isotopic enrichment available along with excellent chemical purity. We consistently review and im-prove our methods for solvent purification and for the reduction of water content in our already high quality NMR solvents. All of our NMR solvents undergo thorough quality control testing during the manufacturing and packaging processes to verify the product quality is preserved.
Most deuterated NMR solvents readily absorb moisture. To minimize the chance of water contamination, use carefully dried NMR tubes and handle NMR solvents in a dry atmosphere.
How to Obtain a Nearly Moisture-free Surface1. Dry glassware at ~150 °C for 24 hours and cool under an inert atmosphere.
2. Rinse the NMR tube with the deuterated solvent prior to preparing the sample. This allows for a complete exchange of protons from any residual moisture on the glass surface.
3. For less demanding applications, a nitrogen blanket over the sample prepara-tion setup may be adequate.
How to Avoid Sources of Impurities and Chemical Residues1. Use clean, dry glassware and PTFE accessories.
2. Use a vortex mixer instead of shaking the tube contents. The latter action can introduce contaminants from the NMR tube cap.
3. Residual chemical vapor from equipment can be a source of impurities; residual acetone in pipette bulbs is a common example.
How to Remove Solvent Residue1. Protonated solvent residue can be removed by co-evaporation.
2. Use a small quantity of the desired deuterated solvent, a brief high vacuum drying (5–10 min), and then prepare the NMR sample.
3. Solvents such as chloroform-d, benzene-d6, and toluene-d8, also remove residual water azeotropically.
How to Avoid TMS Evaporation1. Extended storage of TMS-containing solvents can lead to some loss of TMS.
Storing these solvents in Sure/Seal™ bottles virtually eliminates such a loss.*
2. Purchase TMS-containing solvents in single-use ampules.* To dispense the product from Sure/Seal™ bottle or septum vials, use standard syringe needle techniques. For details and recommended procedures, please refer to Aldrich Technical Bulletin AL-134 or visit our Web site at Aldrich.com.
Use and Handling of NMR Solvents
Aldrich Chemistry also offers unparalleled convenience and service. Our award-winning website allows for quick product searching, easy ordering, and a wealth of valuable tools and information to aid your research efforts. We also offer on-site stocking programs for NMR solvents so they are avail-able to you for immediate use. If you have technical questions, you can feel comfortable knowing our knowledgeable and well-trained technical service specialists can answer your toughest questions.
Try our NMR Solvents today to see their high quality for yourself.
For a complete listing of all NMR-related products and information, visit Aldrich.com/nmr
Stable IsotopesLeslie Patterson, Ph.D.Product Managerleslie.patterson@sial.com
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
23Stable Isotopes
Specialty NMR Solvents Aldrich Chemistry offers a wide range of high purity deuterated solvents for the NMR community. In addition, we also offer various specialty solvents for more demanding applications. Whether you need the high-est enriched deuterium oxide available, or solvents with a reduced HOD peak, we have what you need.
“Special HOH” SolventsWhen customers requested NMR solvents with a suppressed HOD peak we listened, and developed NMR solvents called “Special HOH”. These solvents have an HOD peak which is less than 1% of the HOH peak, to minimize potential exchange with an analyte. “Special HOH” solvents also meet our standard water specification for NMR solvents.
1H-NMR Spectrum of DMSO-d6 “Special HOH”
Anhydrous NMR SolventsWhen water content is of paramount concern, try our anhydrous solvents that contain reduced levels of water.
“Extra” Enriched D2OWith an enrichment of 99.994 atom % D, this is the highest enriched deuterium oxide available.
For additional information visit Aldrich.com/nmr or contact:
Stable Isotope Technical ServicePhone: (937) 859-1808 (800) 448-9760 (US and Canada) Fax: (937) 859-4878 E-mail: isosales@sial.com
11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 –0.5ppm
2.5 2.4ppm
3.3ppm
HOH
DMSO-d6 residual peak
HOD
Deuterium oxide, Extra, 99.994 atom % D613398-10G serum bottle 10 g613398-50G serum bottle 50 g
Acetonitrile-d3, 99.8 atom % D, Anhydrous (water < 10 ppm)569550-10X1ML ampule 10 x 1 mL
Benzene-d6, 99.6 atom % D, Anhydrous (water < 10 ppm)570680-50G glass bottle 50 g
Chloroform-d, 99.8 atom % D, Anhydrous (water < 10 ppm)570699-50G glass bottle 50 g
Dimethyl sulfoxide-d6, 99.9 atom % D, Anhydrous (water < 50 ppm)570672-50G glass bottle 50 g569585-5X1ML ampule 5 x 1 mL569585-10X1ML ampule 10 x 1 mL
Methanol-d4, 99.8 atom % D, Anhydrous (water < 50 ppm)570729-50G glass bottle 50 g569534-5X1ML ampule 5 x 1 mL569534-10X1ML ampule 10 x 1 mL
Toluene-d8, 99.6 atom % D, Anhydrous (water < 10 ppm)570710-50G glass bottle 50 g
Acetonitrile-d3, 99.8 atom % D, "Special HOH"699543-10G glass bottle 10 g699543-25G glass bottle 25 g699543-50G glass bottle 50 g
Dimethyl sulfoxide-d6, 99.9 atom % D, "Special HOH"612324-25G glass bottle 25 g612324-50G glass bottle 50 g612324-100G glass bottle 100 g716731-10x0.75ML ampule 10 x 0.75 mL716731-10ML serum vial 10 mL716731-50ML serum vial 50 mL
Data acquired on a Varian 400 MHz instrument.
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
24
Stockroom ReagentsTodd HalkoskiMarket Segment Manager, Solvents and Reagentstodd.halkoski@sial.com
Sigma-Aldrich® is a Leading Global Supplier and Manufacturer of High Quality, Stockroom and Essential Research Products We specialize in providing the most comprehensive product range and widest selection of purity grades to fulfill your particular application needs.
•Solvents — As a leading supplier of high-purity, research grade solvents, we have the solvent to meet your exact needs
•Acids and Bases — From ACS grade to TraceSELECT® Ultra for the ultra trace analysis level down to ppb and ppt.
• Routine Organic and Inorganic Reagents
• Adsorbents, Filter Aids, and Drying Agents
You will also find several programs that offer unique solutions to help control your costs. One may be right for you!
National Association of Scientific Materials Managers (NAOSMM)Sigma-Aldrich is a proud partner of NAOSMM and its members receive savings on a wide range of Sigma-Aldrich Chemistry products.
Supply Rewards™ ProgramGet rewarded for choosing Sigma-Aldrich. Earn rewards for your team, your community, or yourself, every time you purchase selected products from Sigma-Aldrich. With over 1,500 eligible common laboratory products to choose from, earning reward points couldn't be easier.
New Lab Start-Up ProgramGet your new lab set up in an easy and economical way. Your lab is eligible for the program if:
• You are starting a new lab
• You are moving to a new location
• You have received your first research grant
To learn more, visit Aldrich.com/stockroom
By always listening, Sigma-Aldrich delivers.Monthly Savings from Sigma-Aldrich
Easy-to-find site offers monthly savings on Chemistry, Life Science, Analytical, and Labware products.
United States Aldrich.com/offers
Europe Aldrich.com/offerseu
For specific country discounts, visit us at Aldrich.com
The Sigma-Aldrich Pressure-Temperature Nomograph allows you to quickly and easily estimate boiling points at various pressures. Interactive controls simplify calculations to improve the efficiency of your distillation or evaporation process.
Pressure Conversion Tab: Use the built-in Pressure Conversion Calculator to convert among five units of pressure using either numeric values or scientific notation.
Temperature Conversion Tab: Quickly calculate temperature conversions without leaving the Nomograph.
Printable: Need a hard copy to take with you? Simply right-click and select 'print'.
Aldrich.com/nomograph
Stockroom Reagents
Need a Molarity Calculator for your Acid/Base solutions?
Aldrich Normality and Molarity Calculator
Features• Calculates molarity for known acids and bases
• Calculates solutions of a solid reagent
• Dilutes a solution of known molarity
• Gets results at the click of a button
• Runs on your iPhone® and iPad® mobile digital devices
Benefits• Saves time over hand calculations
• Increases accuracy of calculations
Easy-to-Use 1. Select Acid or Base from drop down menu
2. Density, FW, and Wt. % will auto-populate
3. Input desired volume and concentration
4. Click on “Calculate”
Add Aldrich to save time and access the Normality and Molarity Calculator atAldrich.com/calculator
iPhone and iPad are trademarks of Apple Inc., registered in the US and other countries. 76070
76070 ALD Molarity Calc ad_R.indd a 7/29/2011 2:22:51 PM
TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
26
Labware NotesPaula FreemantleProduct Managerlabware@sial.com
Aldrich® Rotary Evaporator Replacement Glassware•Cross-referenced with Buchi part numbers
•Plastic-coated and uncoated versions
•Jointed flasks compatible with most evaporators
This heavy-duty glassware is designed to fit Buchi rotary evaporators and is cross-referenced with Buchi part numbers to aid in selection. The condensers and flasks are available in non-coated glass for maximum resistance to solvents and heat, and with poly coating for extra protection from breakage. The jointed flasks and splash-guard adapters will fit most brands of rotary evaporators. Note that 35/20 and 35/25 spherical joint components are interchangeable.
Premium quality glassware, widest range, low cost
•Condenser Assemblies and Components
•Drying Flasks with Indents
•Evaporating Flasks, Pear-Shape
•Large Evaporator Flasks
•Receiving Flasks Adapters
•Receiving Flasks
•Splash Guard Adapters
•Vapor Duct Tubes
To see the complete range of products or to place orders, visit Aldrich.com/evapglass
Z682055
Z515515
Z549193
Z682187
Z682713
Z682829
Z682918
Z682411
Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
27Labware Notes
News and Innovation
Aldrich® FKM sleeve stopper septaThese new septa are made from fluoroelastomer FKM which is highly resistant to a broad range of solvents. An elastomer study done at Sigma-Aldrich compared the solvent compatibility (resistance) of FKM and EPDM rubber (Figure 1). A Sealability Factor was determined for each elastomer. The lower the number the more compatible the rubber is with a solvent.
Z569941 10/30 jointsZ569968 14/20 joints, 2, 4, and 8 oz Aldrich bottlesZ569976 15/25 joints, 10, 32, 40 oz, 1 L Aldrich bottles,
125 mL, 1 L Sure/Seal bottlesZ569984 24/40 joints, 64, 80 oz, and 1 gal Aldrich jugs
Aldrich Rotary Evaporator Adapter SetThis versatile adapter connects jars and bottles to the vapor tube of a rotary evaporator. Precision machined from durable, chemically inert glass-filled PTFE. The unique, “universal fit” threaded connection adapts to any suitable cap. Simply insert the threaded shaft of the adapter through a 16 mm diam-eter holed cap and secure by hand-tightening the PTFE gasket and nut. Attach the other end of the adapter to the vapor tube via standard taper joint and clip. Set includes one 58 x 400 mm diameter holed cap and a solid top cap with PTFE liners, and a 200 mL borosilicate glass jar.
Z723169-1EA 24/40 joint Z723177-1EA 29/32 joint
Julabo® Economy Series Refrigerated/Heating Circulators•Compact design
•Temp. range -20 to 100 °C
•0.35 bar pump pressure
•15 L/min pump flow
•Cooling capacity 120 W, at 0 °C
•200 W, at 20 °C
•Heater capacity 2 kw
•Bath opening W × L × D 15 cm × 16 cm × 13 cm
•Overall W × L × H 20 cm × 36 cm × 56 cm
•Volume 4.5 L
Z557285-1EA 115 VAC Z653209-1EA 230 VAC
Figure 1
Sealability FactorThe lower the number the higher the compatibility
0500
10001500200025003000350040004500
Diethyl ether
Dichloromethane
Benzene
Cyclohexanes
Diisopropylamine
Fluoroelastomer FKM
EPDM rubber
Sigma-Aldrich3050 Spruce StreetSt. Louis, MO 63103 USA
Sigma-Aldrich® Worldwide Offices
Order/Customer Service (800) 325-3010 • Fax (800) 325-5052 Technical Service (800) 325-5832 • sigma-aldrich.com/techservice Development/Custom Manufacturing Inquiries (800) 244-1173 Safety-related Information sigma-aldrich.com/safetycenter
World Headquarters 3050 Spruce St.
St. Louis, MO 63103 (314) 771-5765
sigma-aldrich.com
Enabling Science to Improve the Quality of Life
ArgentinaFree Tel: 0810 888 7446 Tel: (+54) 11 4556 1472 Fax: (+54) 11 4552 1698
AustraliaFree Tel: 1800 800 097 Free Fax: 1800 800 096 Tel: (+61) 2 9841 0555 Fax: (+61) 2 9841 0500
AustriaTel: (+43) 1 605 81 10 Fax: (+43) 1 605 81 20
Belgium Tel: (+32) 3 899 13 01 Fax: (+32) 3 899 13 11BrazilFree Tel: 0800 701 7425 Tel: (+55) 11 3732 3100 Fax: (+55) 11 5522 9895
CanadaFree Tel: 1800 565 1400 Free Fax: 1800 265 3858 Tel: (+1) 905 829 9500 Fax: (+1) 905 829 9292
ChileTel: (+56) 2 495 7395 Fax: (+56) 2 495 7396
People’s Republic of ChinaFree Tel: 800 819 3336 Tel: (+86) 21 6141 5566 Fax: (+86) 21 6141 5567
Czech RepublicTel: (+420) 246 003 200 Fax: (+420) 246 003 291
DenmarkTel: (+45) 43 56 59 00 Fax: (+45) 43 56 59 05
FinlandTel: (+358) 9 350 9250 Fax: (+358) 9 350 92555
FranceFree Tel: 0800 211 408 Free Fax: 0800 031 052 Tel: (+33) 474 82 28 88 Fax: (+33) 474 95 68 08
GermanyFree Tel: 0800 51 55 000 Free Fax: 0800 64 90 000 Tel: (+49) 89 6513 0 Fax: (+49) 89 6513 1169
Hungary Tel: (+36) 1 235 9055 Fax: (+36) 1 235 9068IndiaTelephone Bangalore: (+91) 80 6621 9400 New Delhi: (+91) 11 4358 8000 Mumbai: (+91) 22 4087 2364 Pune: (+91) 20 4146 4700 Hyderabad: (+91) 40 3067 7450 Kolkata: (+91) 33 4013 8000
Fax Bangalore: (+91) 80 6621 9550 New Delhi: (+91) 11 4358 8001 Mumbai: (+91) 22 2579 7589 Pune: (+91) 20 4146 4777 Hyderabad: (+91) 40 3067 7451 Kolkata: (+91) 33 4013 8016
IrelandFree Tel: 1800 200 888 Free Fax: 1800 600 222 Tel: +353 (0) 402 20370 Fax: + 353 (0) 402 20375
IsraelFree Tel: 1 800 70 2222 Tel: (+972) 8 948 4222 Fax: (+972) 8 948 4200
Italy Free Tel: 800 827 018 Tel: (+39) 02 3341 7310 Fax: (+39) 02 3801 0737
JapanTel: (+81) 3 5796 7300 Fax: (+81) 3 5796 7315
KoreaFree Tel: (+82) 80 023 7111 Free Fax: (+82) 80 023 8111 Tel: (+82) 31 329 9000 Fax: (+82) 31 329 9090
LuxembourgTel: (+32) 3 899 1301 Fax: (+32) 3 899 1311
MalaysiaTel: (+60) 3 5635 3321 Fax: (+60) 3 5635 4116
MexicoFree Tel: 01 800 007 5300 Free Fax: 01 800 712 9920 Tel: (+52) 722 276 1600 Fax: (+52) 722 276 1601
The Netherlands Tel: (+31) 78 620 5411 Fax: (+31) 78 620 5421
New ZealandFree Tel: 0800 936 666 Free Fax: 0800 937 777 Tel: (+61) 2 9841 0555 Fax: (+61) 2 9841 0500
NorwayTel: (+47) 23 17 60 00 Fax: (+47) 23 17 60 10
PolandTel: (+48) 61 829 01 00 Fax: (+48) 61 829 01 20
PortugalFree Tel: 800 202 180 Free Fax: 800 202 178 Tel: (+351) 21 924 2555 Fax: (+351) 21 924 2610
RussiaTel: (+7) 495 621 5828 Fax: (+7) 495 621 6037
SingaporeTel: (+65) 6779 1200 Fax: (+65) 6779 1822
SlovakiaTel: (+421) 255 571 562 Fax: (+421) 255 571 564
South AfricaFree Tel: 0800 1100 75 Free Fax: 0800 1100 79 Tel: (+27) 11 979 1188 Fax: (+27) 11 979 1119
SpainFree Tel: 900 101 376 Free Fax: 900 102 028 Tel: (+34) 91 661 99 77 Fax: (+34) 91 661 96 42
SwedenTel: (+46) 8 742 4200 Fax: (+46) 8 742 4243
SwitzerlandFree Tel: 0800 80 00 80 Free Fax: 0800 80 00 81 Tel: (+41) 81 755 2511 Fax: (+41) 81 756 5449
ThailandTel: (+66) 2 126 8141 Fax: (+66) 2 126 8080
United KingdomFree Tel: 0800 717 181 Free Fax: 0800 378 785 Tel: (+44) 1747 833 000 Fax: (+44) 1747 833 313
United StatesToll-Free: 800 325 3010 Toll-Free Fax: 800 325 5052 Tel: (+1) 314 771 5765 Fax: (+1) 314 771 5757
VietnamTel: (+84) 8 3516 2810 Fax: (+84) 8 6258 4238
Internet sigma-aldrich.com
NNC 75951-512040
1081
©2011 Sigma-Aldrich Co. LLC. All rights reserved. SIGMA, SAFC, SIGMA-ALDRICH, ALDRICH, SUPELCO, ISOTEC, and TRACESELECT are trademarks of Sigma-Aldrich Co. LLC, registered in the US and other countries. ChemFiles, Add Aldrich, MolarMatic, and Sure/Seal are trademarks of Sigma-Aldrich Co. LLC. Journal Citation Reports is a registered trademark of Thomson Reuters (Scientific) Inc. ChiroSolv® and EnantioPrep are trademarks of ChiroSolve, Inc. iPhone and iPad are trademarks of Apple Inc., registered in the US and other countries. Paxil is a registered trademark of GlaxoSmithKline LLC. Zoloft is a registered trademark of Pfizer Inc. XtalFluor-E and XtalFluor-M are registered trademarks of OmegaChem Inc. SciFinder is a registered trademark of the American Chemical Society. BASIL is a trademark of BASF. Julabo is a registered trademark of Julabo USA Inc. SUPPLY REWARDS is a trademark of Supply Rewards. Sigma brand products are sold through Sigma-Aldrich, Inc. Purchaser must determine the suitability of the product(s) for their particular use. Additional terms and conditions may apply. Please see product information on the Sigma-Aldrich website at www.sigmaaldrich.com and/or on the reverse side of the invoice or packing slip.