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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
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Introduction 3
Aldrich
Haydn Boehm, Ph. D.
Global Marketing Manager: Chemical Synthesis
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 Corporation
6000 N. Teutonia Ave.Milwaukee, WI 53209 USA
Editorial TeamHaydn Boehm, Ph.D.Wesley Smith
Dean Llanas
Sharbil J. Firsan, Ph.D.
Weimin Qian
Production Team
Cynthia Skaggs
Vincent Clark
Chris Lein
Tom Beckermann
Christian Hagmann
Denise de Voogd
Chemistry Team
Leslie 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 HalkoskiPaula Freemantle
Mike Willis
Aldrich ChemFiles Subscriptions
To request your FREE subscription to Aldrich ChemFiles visit
Aldrich.com/chemfiles or contact your local Sigma-Aldrich office
(see back cover).
Aldrich ChemFiles Online
Aldrich ChemFiles is also available in PDF format
at Aldrich.com/chemfiles.
Aldrich Chemistry Products
Aldrich brand products are sold through Sigma-Aldrich, Inc.
Sigma-Aldrich, Inc. warrants that its products conform to the
information contained in this and other Sig ma-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 Services
Contact 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 Contents
Synthetic Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Catalysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Organometallics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Building Blocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Specialty Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Stable Isotopes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Stockroom Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Labware Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
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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 uniquereagent 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% ofchiral 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 384
separation conditions
Recover racemate using
recovery solution
Check purity
and yield
Heat, Cool
Repeat until targetenantiomeric purity
is achieved
Purify racemate using the
best separation condition
Extract purified
enantiomer ready
for testing
The experiment involves Three phases of work:
1. Screening: Racemate is screened against 384 different combinationsof 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
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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 intoneutral 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 Kits
Acid
The 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
Base
The 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
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8
Case Studies with ChiroSolv®
EnantioPrep™ Solution
ChiroSolv EnantioPrep kits were used fortwo 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. Theyield 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 dialkylaminodifluorosulfinium
tetrafluoroborate salts. They are useful for the deoxofluorination
of hydroxyl and carbonyl moieties when used in conjunction with apromoter.*
Advantages of XtalFluor salts
Aldrich XtalFluor Reagents
H3C
H3C N=SF2 BF4
– –
ON=SF
2 BF
4
+ +
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/xtalfluors
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
deoxofluorination reagents
• Broad substrate scope
• Predictable and high
chemoselectivity
sh4078
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10
Recap: How to Use ChiroSolv® Kits
1. 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 aunique barcode.
Each vial contains aunique combination of
resolving agent/solvent—8 types of kits give 768 such
combinations.
Pierceable septa or foilseal for easy
robotic manipulation.
Plastic sleeve holdsthe vials together evenwhen they are out of
the rack.
Each vial has a uniquealphanumeric identification.
Rack, vials, and septaare chemically inertand can withstand–20 °C to 120 °C.
Extra septum matprovided in kits for
solid racemates.
Product Information for Liquid RacematesProduct No. Product Name/Description
681431 ChiroSolv Resolving Kit, Acid Series 1
681423 ChiroSolv Resolving Kit, Acid Series 2
681415 ChiroSolv Resolving Kit, Acid Series 3699217 ChiroSolv Resolving Kit, Acid Series 4
700363 ChiroSolv Resolving Kit, Complete Acid Series
681407 ChiroSolv Resolving Kit, Base Series 1
681393 ChiroSolv Resolving Kit, Base Series 2
681377 ChiroSolv Resolving Kit, Base Series 3
699241 ChiroSolv Resolving Kit, Base Series 4
700371 ChiroSolv Resolving Kit, Complete Base Series
Product Information for Solid Racemates
Product No. Product Name/Description
698881 ChiroSolv Resolving Kit, Acid Series 1
699527 ChiroSolv Resolving Kit, Acid Series 2
698873 ChiroSolv Resolving Kit, Acid Series 3
699225 ChiroSolv Resolving Kit, Acid Series 4
700398 ChiroSolv Resolving Kit, Complete Acid Series
699233 ChiroSolv Resolving Kit, Base Series 1
698938 ChiroSolv Resolving Kit, Base Series 2
698946 ChiroSolv Resolving Kit, Base Series 3
698954 ChiroSolv Resolving Kit, Base Series 4
700401 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 vialswith crystals for
specific rotation
Select vials with crystals ¬e 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
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Need a MolarMatic™
Measuring Cylinders
for 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
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20
Specialty SynthesisPietro Butti, Ph.D.
Product Manager
Ionic Liquids: A Smart Alternative
Environmentally 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 compoundsproduced 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 fromacademia 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
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
1 9 9 0
1 9 9 1
1 9 9 2
1 9 9 3
1 9 9 4
1 9 9 5
1 9 9 6
1 9 9 7
1 9 9 8
1 9 9 9
2 0 0 0
2 0 0 1
2 0 0 2
2 0 0 3
2 0 0 4
2 0 0 5
2 0 0 6
2 0 0 7
2 0 0 8
2 0 0 9
2 0 1 0
Year
N u m b e r o f P u b i c a t i o n s
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 N
H
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 ofpotential applications in which this class of extraordinary compounds can
be used.
Publications per Years
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TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
22
Aldrich NMR Solvents
Challenge Us… And See Why Our Quality isUnsurpassed!
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 andwork 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 ofwater contamination, use carefully dried NMR tubes and handle NMR solvents in adry atmosphere.
How to Obtain a Nearly Moisture-free Surface
1. 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 onthe 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 Residues
1. Use clean, dry glassware and PTFE accessories.
2. Use a vortex mixer instead of shaking the tube contents. The latter action canintroduce 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 Residue
1. Protonated solvent residue can be removed by co-evaporation.
2. Use a small quantity of the desired deuterated solvent, a brief high vacuumdrying (5–10 min), and then prepare the NMR sample.
3. Solvents such as chloroform-d, benzene-d6, and toluene-d8, also removeresidual water azeotropically.
How to Avoid TMS Evaporation
1. 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 standardsyringe needle techniques. For details and recommended procedures, pleaserefer 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 Manager
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Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
2Stable 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” Solvents
When 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 Solvents
When water content is of paramount concern, try our anhydrous
solvents that contain reduced levels of water.
“Extra” Enriched D2O
With 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 Service
Phone: (937) 859-1808
(800) 448-9760 (US and Canada)
Fax: (937) 859-4878
E-mail: [email protected] 1 1. 5 11 .0 1 0. 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. 5
ppm
2 .5 2 .4ppm
3.3
ppm
HOH
DMSO-d6residual peak
HOD
Deuterium oxide, Extra, 99.994 atom % D
613398-10G serum bottle 10 g
613398-50G 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 g
569585-5X1ML 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 g
569534-5X1ML ampule 5 x 1 mL
569534-10X1ML 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 g
699543-25G glass bottle 25 g
699543-50G glass bottle 50 g
Dimethyl sulfoxide-d6, 99.9 atom % D, "Special HOH"
612324-25G glass bottle 25 g
612324-50G glass bottle 50 g
612324-100G glass bottle 100 g
716731-10x0.75ML ampule 10 x 0.75 mL
716731-10ML serum vial 10 mL
716731-50ML serum vial 50 mL
Data acquired on a Varian 400 MHz instrument.
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24
Stockroom Reagents Todd Halkoski
Market Segment Manager, Solvents and Reagents
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™ Program
Get 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 Program
Get 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
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Need a MolarityCalculator foryour Acid/Basesolutions?
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 at
Aldrich.com/calculator
iPhone and iPad are trademarks of Apple Inc., registered in the US and other countries. 76070
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TO ORDER: Contact your local Sigma-Aldrich office (see back cover), or visit Aldrich.com/chemicalsynthesis.Aldrich.com
26
Labware NotesPaula Freemantle
Product Manager
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 evaporatorsand 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
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Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact your local Sigma-Aldrich office, or visit safcglobal.com.
2Labware Notes
News and Innovation
Aldrich® FKM sleeve stopper septa
These 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 joints
Z569968 14/20 joints, 2, 4, and 8 oz Aldrich bottles
Z569976 15/25 joints, 10, 32, 40 oz, 1 L Aldrich bottles,
125 mL, 1 L Sure/Seal bottles
Z569984 24/40 joints, 64, 80 oz, and 1 gal Aldrich jugs
Aldrich Rotary Evaporator Adapter Set
This 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 × H20 cm × 36 cm × 56 cm
• Volume 4.5 L
Z557285-1EA 115 VAC
Z653209-1EA 230 VAC
Figure 1
Sealability Factor The lower the number the higher the compatibility
0
500
1000
1500
2000
25003000
3500
4000
4500
D i e t h y l e t h e r
D i c h l o r o m e t h a n e
B e n z e n e
C y c l o h e x a n e s
D i i s o p r o p y l a m i n e
Fluoroelastomer FKM
EPDM rubber
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Sigma-Aldrich
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