Universität Erlangen-Nürnberg, Institut für Organische Chemie

NMR Department

NMR Solvents

Usage, Purification and More

Solvents Available

Any standard solvents may be obtained from the NMR operators. There are currently in stock:

Solvent Price (EUR/g)

CDCl₃ 0.08

DMSO-d₆ 0.56

CD₃CN 1.20

Acetone- d₆ 0.82

C₆D₆ 1.07

CD₃NO₂ 2.00

THF-d₈ 5.90

CD₂Cl₂ 2.60

Toluene-d₈ 2.25

CF₃COOD 1.16

DMF-d₇ 13.00

Pyridine-d₅ 11.85

C₆D₅NO₂ 3.60

D₂O 0.93

CD₃OD 1.82

CH₃OD 1.68

CD₃COOD 5.26

Solvent	Price (EUR/g)
CDCl₃	0.08
DMSO-d₆	0.56
CD₃CN	1.20
Acetone- d₆	0.82
C₆D₆	1.07
CD₃NO₂	2.00
THF-d₈	5.90
CD₂Cl₂	2.60
Toluene-d₈	2.25
CF₃COOD	1.16
DMF-d₇	13.00
Pyridine-d₅	11.85
C₆D₅NO₂	3.60
D₂O	0.93
CD₃OD	1.82
CH₃OD	1.68
CD₃COOD	5.26

Special solvents, lanthanide shift reagents (chiral, achiral), and special reagents like chiral solvents are available on request.

Properties

Here you can look up properties of deuterated solvents (¹H-, ¹³C-chemical shifts, water signal chemical shift, melting-, boiling points, prices; in German). This table was kindly provided by Fritz Kastner, University of Regensburg.

Standards

Here you can look up often employed standards in NMR spectroscopy (in German). This table was kindly provided by Fritz Kastner, University of Regensburg.

Usage

The following is an outline by Prof. J. A. Gladysz about usage of diverse solvents with respect to special demands of the Gladysz group.

One of the painfully-learned lessons of research is "never to trust the purity of any starting material" or "assay everything". Since the NMR lab is used to sensitive RLi compounds, we are probably in very good hands. Most rhenium compounds are in fact not very water/O₂ sensitive. However, many of our phosphines rapidly form phosphine oxides in solvent with O₂ traces. There will be other projects with very sensitive species.

Some general recommendations are as follows:

Toluene-d₈ Very good for low temperature and high temperature work

Benzene-d₆ We have a lot of data in this solvent, which is cheaper than toluene-d₈. However, it is not my favorite since chemical shifts can be very different from chlorinated solvents.
A lot of carbon chain complexes have been measured in benzene.

Chlorobenzene-d₅ A very good solvent, not too expensive. It freezes at -45 degrees, limiting low temp work. However, it is high boiling. More polar than benzene/toluene, which is what you like.

C₆D₅CF₃ This would be a valuable deuterated solvent, and Ralf Meier has researched the best method. We should have someone make it.

CDCl₃ This solvent (USA purity) has a good record with us. It usually will dissolve cations.

CD₂Cl₂ This solvent is excellent. It doesn't freeze until -98 degrees, and is ideal for low temperature exploratory chemistry. We often use CH₂Cl₂ and just monitor by phosphorus. The -d₂ solvent is much more expensive, but is a cost we have to swallow in our research.

CDFCl₂ Another outstanding solvent that can be used down to -140 degrees. It must be prepared, the reference is #18 in paper #143, see Figure 1 for some typical data. You can detect all sorts of isomers at such low temps; the prep is not too expensive.
***note: the above halogenated solvents CAN be used to monitor RLi/RMgX reactions; almost always the organometallic compound will react faster than the solvent****

Acetone-d₆ This is a fine solvent, not too expensive, although not as polar as others given below (something soluble in acetone is almost always soluble in a halogenated solvent)

CD₃CN This is usually the #1 choice when a more polar solvent is needed. If the solvent reaction with the metal complex, one usually gets a well defined (previously prepared) complex

DMSO-d₆ This is usually a poor choice. Don't let a NMR technician use it by default. It is not expensive (hence popular), but if you look at nucleophilicity scales MeSMe and DMSO are among the most aggressive ligands for metals. And DMSO can give oxidation -or- substitution product. So when things go wrong, you get a big big mess.

CD₃NO₂ This is a reactive solvent, but I have had some good luck with it from time to time, for example with poorly soluble complexes. It is very polar.

THF-d₈ This solvent hasn't been used very much in the group. The major reason is that rhenium cations aren't very soluble in ethers. It is also expensive. However, we have used it for following RLi additions, it has worked well.

As a final comment: All expensive NMR solvents that do not become very contaminated by other NMR solvents can be recovered. In particular, prep GC allows 0.1 to 0.3 mL injections. One could set up one of the old prep GC's to do this job.

Purification of Specific Solvents

The following section is adapted from Shriver and Drezdzon, The Manipulation of Air-Sensitive Compounds, Wiley, New York 1986.

A. Water.

Purging with inert gas or pumping on this solvent will rid it of dissolved oxygen. Dissolved salts may be removed by distillation or by utilizing a commercially available deionizing system.

B. Saturated Hydrocarbons.

Purging and freeze-pump-thaw methods are effective in degassing paraffins. Distillation with the elimination of the first fractions produces dry solvent. Molecular sieves may also be used to remove water. Distillation from sodium-benzophenone ketyl is highly effective in obtaining very low levels of water and oxygen. Commercial grades of hydrocarbons are often contaminated with olefins, which can be eliminated by several washings with concentrated sulfuric acid, separation from the acid, washing with water, and, after preliminary drying with molecular sieves 4Å or 5Å, subjecting the solvent to fresh desiccant or one of the drying procedures outlined above.

C. Aromatic Hydrocarbons.

The methods listed for saturated hydrocarbons may be used with benzene. Thiophene and similar sulfur-containing impurities are removed by sulfuric acid washes. Very-high-purity benzene may be prepared by fractional crystallization from ethanol followed by distillation. Toluene and xylenes are purified in the same manner as benzene; however, these solvents should be kept cool (at or below room temperature) during sulfuric acid treatment due to their greater reactivity toward sulfonation.

D. Chlorocarbons.

Molecular sieves provide a good means of drying these materials. CAUTION: Strong reducing agents, such as metal hydrides, Na and Na-K, react violently with halogenated hydrocarbons and should never be used to dry these materials. Chloroform generally contains 1% ethanol to suppress phosgene formation. This may be removed by shaking with concentrated H₂SO₄, separating from the acid, washing with water, predrying with molecular sieves or silica gel, drying with molecular sieve 4Å, and distilling, taking the central fraction. This material must be used directly or stored strictly out of contact with the atmosphere. Methylene chloride is less reactive than chloroform and is not prone to phosgene formation. It may be distilled from P₂O₅ or dried with molecular sieves and distilled under an inert atmosphere. (Note that traces of phosphine are introduced into a material by the use of P₂O₅.)

E. Ethers.

Diethyl ether is available in very dry grades, which for most purposes can be used directly from the freshly opened can. Similarly, purified grades of tetrahydrofuran are available which are often sufficiently dry be used directly (Fisher). When extremely sensitive materials are handled, diethyl ether and tetrahydrofuran are often distilled from LiAlH. However, great care must be taken first to remove all peroxides and never to let the still pot go dry. Sodium-benzophenone ketyl is also effective with ethers which are peroxide free, and it has the advantage of being safer than LiAlH4. A small amount of benzene is introduced into the solvent when sodium-benzophenone ketyl is used.

F. Nitriles.

Acetonitrile is a convenient solvent for many ionic compounds, but it is extremely difficult to dry to much better than millimolar in water. In addition, degradation products of the solvent, ammonia and acetic acid, may be present. Strongly acidic or basic drying agents react with this solvent and strong reducing agents are ruled out. One recommended procedure is first to predry the solvent with molecular sieves or silica gel if large quantities of water are present,¹ then to stir or shake this material with calcium hydride, which will remove both acetic acid and water. The predried acetonitrile is then distilled at a high reflux ratio from P₂O₅ (less than 5 g/L) under an inert atmosphere. A gel may form in the distillation flask, and care should be taken to leave behind the bulk of the solvent and residues in the distillation flask. The solvent is then refluxed over calcium hydride and distilled under an inert atmosphere using a high reflux ratio and a good fractionating column. The middle fraction is collected. Acrilonitrile is an impurity which will contaminate the product if this distillation is not efficient.

As an alternative to this procedure, some workers advocate stirring acetonitrile with calcium hydride, distilling it under a dry inert atmosphere, and passing it through a highly activated alumina column under a dry inert atmosphere.

G. Alcohols.

The removal of traces of water from methanol and ethanol is difficult. Calcium turnings, magnesium turnings activated with iodine, and lump calcium hydride are sometimes used to remove traces of water from methanol. However, these active metals may contain some nitride and give rise to contamination by ammonia. These same drying agents may be used with higher alcohols. A column of dry molecular sieve 4Å is also effective in removing water from ethanol and higher alcohols.

H. Acetone.

Acetone is very difficult to dry, since many of the usual drying agents cause reaction, including MgSO₄. Storage over molecular sieve 4Å yields relatively dry acetone. High-purity acetone may be obtained by saturating the solvent with dry NaI at room temperature, decanting and cooling to -10^oC, isolating the crystals which form (NaI-acetone complex), warming the crystals to room temperature, and distilling the resulting liquid.

¹J. F. Coetzee, Pure and Appl. Chem., 13, 429-433 (1966).

Personal Experiences on Purity and Purification Processes (WB)

We are frequently working on organoalkali compounds, so some comments seem to be indicated.

For small amounts of deuterated THF, diethyl ether, benzene, and toluene, we found that sodium-lead alloy is a very convenient drying agent. Put an appropriate amount in a dry flask (ca. 20 ml) equipped with a teflon cock and rubber septa, evacuate and (preferably) heat under vacuum with a heat gun, flush with dry argon or nitrogen, then fill in the solvent (taken from an ampoule, preferably under argon) by means of a plastic syringe. Caution: THF may swell the syringe within a few minutes, so quick work is indicated. Water contents manifest in small hydrogen bubbles. Storing one or several days will remove residual water to an amount tolerable for virtually all purposes. Due to alloyed lead, the sodium surface is regenerated continuously. Sodium lead alloy may be safely destroyed by water (of course, hydrogen will evolve, so remove any fire sources).

Solvents from ampoules are strongly prefered over bottled solvents. I once achieved THF-d₈ in a screw bottle, the water contents were extremely high, resulting in vigorous hydrogen evolution.

Prolongued exposure of a solvent to NMR rubber caps will swell the cap, eventually letting the solvent evaporate. Of course, the best choice is to seal an NMR tube for samples expected to be studied over longer periods. However, a very good though somewhat expensive alternative is to use NMR tubes equipped with screw caps (DM 40 per piece). These caps (teflon) provide a very good seal as long as they are not punctured. I have a sample of vinyllithium in THF-d₈ in such a tube, prepared in 1991, which is still ok and is kind of a reference sample in our studies!

I confirm the above remarks by Shriver concerning acetone. Even small traces of acid or base will lead to reaction (self-condensation), leading to diacetone alcohol in the first step which manifests in 3 (at first strange) singlets in the ¹H-NMR spectrum. In the presence of acid, water elimination follows leading to mesityl oxide.

Back to NMR Department Home Page

NMR Department
Institute of Organic Chemistry
Location: Rooms U34, U35, U36
University of Erlangen-Nürnberg
Henkestrasse 42
D-91054 Erlangen, Germany
Phone +49-9131-85-22987
FAX +49-9131-85-22991
e-mail: bauer@chemie.uni-erlangen.de

May 09, 2007 by Walter Bauer

Toluene-d₈	Very good for low temperature and high temperature work
Benzene-d₆	We have a lot of data in this solvent, which is cheaper than toluene-d₈. However, it is not my favorite since chemical shifts can be very different from chlorinated solvents. A lot of carbon chain complexes have been measured in benzene.
Chlorobenzene-d₅	A very good solvent, not too expensive. It freezes at -45 degrees, limiting low temp work. However, it is high boiling. More polar than benzene/toluene, which is what you like.
C₆D₅CF₃	This would be a valuable deuterated solvent, and Ralf Meier has researched the best method. We should have someone make it.
CDCl₃	This solvent (USA purity) has a good record with us. It usually will dissolve cations.
CD₂Cl₂	This solvent is excellent. It doesn't freeze until -98 degrees, and is ideal for low temperature exploratory chemistry. We often use CH₂Cl₂ and just monitor by phosphorus. The -d₂ solvent is much more expensive, but is a cost we have to swallow in our research.
CDFCl₂	Another outstanding solvent that can be used down to -140 degrees. It must be prepared, the reference is #18 in paper #143, see Figure 1 for some typical data. You can detect all sorts of isomers at such low temps; the prep is not too expensive. *note: the above halogenated solvents CAN be used to monitor RLi/RMgX reactions; almost always the organometallic compound will react faster than the solvent**
Acetone-d₆	This is a fine solvent, not too expensive, although not as polar as others given below (something soluble in acetone is almost always soluble in a halogenated solvent)
CD₃CN	This is usually the #1 choice when a more polar solvent is needed. If the solvent reaction with the metal complex, one usually gets a well defined (previously prepared) complex
DMSO-d₆	This is usually a poor choice. Don't let a NMR technician use it by default. It is not expensive (hence popular), but if you look at nucleophilicity scales MeSMe and DMSO are among the most aggressive ligands for metals. And DMSO can give oxidation -or- substitution product. So when things go wrong, you get a big big mess.
CD₃NO₂	This is a reactive solvent, but I have had some good luck with it from time to time, for example with poorly soluble complexes. It is very polar.
THF-d₈	This solvent hasn't been used very much in the group. The major reason is that rhenium cations aren't very soluble in ethers. It is also expensive. However, we have used it for following RLi additions, it has worked well.