Chromatography Forum

With the recent discussions about THF use as a mobile phase component, I was wondering how others ensure that peroxides do not form in their unstabilized THF during use for HPLC-UV. Do you blanket headspace with nitrogen, test with peroxide strips? And what about disposal of non-used THF, and of mixed mobile phase? Is there any level of safety in the HPLC reservoir in pre-mixing the THF with water (or acetic acid-water) and delivering it to the column that way? Sorry, but sometimes THF is just required for the separations, otherwise we'd just avoid it. Thanks.

I have not heard of THF MPs exploding. Does this ever happen?

Peroxide Forming Compounds

Many liquid organic compounds, a few solid and gaseous organic compounds and a few inorganic solids form peroxides upon storage. Most organic peroxides are sensitive to shock, heat or friction to varying degrees. These compounds form by the reaction of the chemical with oxygen allowed in the head space of chemical containers once the container is opened for the first time. Peroxides form at varying rates depending upon the compound. Some peroxides quickly build up to an
explosive level and some are only explosive on concentration, such as when a solvent is distilled.

Although there is no agreement upon what level of peroxides present a significant hazard, several sources suggest that the "safe" range of peroxide formation is 100 ppm or less. It is recommended that all peroxide forming chemicals be tested at the end of the appropriate storage period (see below). If peroxides are detected at a level above 100 ppm, the material must be decontaminated with standard procedures for deperoxidation or discarded as hazardous waste if the material can
not be drain disposed. Test strips for the detection of peroxides may be purchased from lab supply houses.


Control and Safe Use of Peroxide Formers

Peroxide formation may be controlled by the following methods:

Date all incoming containers of peroxide formers when received and again when opened. Many chemical companies now routinely print an expiration date on containers of the worst peroxide formers.
Purchase the smallest possible container size for your needs.
Store peroxide formers in sealed, air-impermeable containers such as dark amber glass with a tight-fitting cap.

Iron inhibits the formation of peroxides in some materials, which is why diethyl ether and some other materials are purchased in metal cans. Ground glass stoppered bottles and plastic containers are not advisable, however, plastic squeeze bottles may be used for small quantities of some materials, such as 2-propanol, for immediate use.

Store peroxide formers in the dark.

Inhibitors are added to some chemicals and the purchase of peroxide formers with added inhibitors is encouraged.

Store peroxide formers, especially those in Table A below, under nitrogen or other inert gas or keep and use them in an inert atmosphere chamber. Note: Some inhibitors actually need small amounts of oxygen to prevent peroxide formation and it is recommended that inhibited chemicals are not stored under an inert atmosphere

Avoid the distillation of peroxide formers without first testing for the existence of peroxides in the material. Most explosions with the use of peroxide formers occur when a material is distilled to dryness. Leave at least 10-20% bottoms. Stir such distillations with a mechanical stirrer or an inert gas. Air or an oxygen containing mixture should never be used for this purpose.

Safe Storage Periods for Peroxide Formers

Unopened chemicals from manufacturer: 18 months
Opened containers: Chemicals in Table A. 3 months
Chemicals in Tables B. and D. 12 months
Uninhibited chemicals in Table C. 24 hours
Inhibited chemicals in Table C. (Do not store under an inert atmosphere) 12 months

A. Chemicals that form explosive levels of peroxides without concentration.

Butadiene a
Isopropyl ether
Potassium amide
Tetrafluoroethylene a
Chloroprene a
Potassium metal
Sodium amide (sodamide)
Vinylidene chloride
Divinylacetylene


B. Chemicals that form explosive levels of peroxides on concentration

Acetal
Diacetylene
2-Hexanol
2-Phenylethanol
Acetaldehyde
Dicyclopentadiene
Methylacetylene
2-Propanol
Benzyl alcohol
Diethyl ether
3-Methyl-1-butanol

Tetrahydrofuran

2-Butanol
Diethylene glycol dimenthyl ether
Methylcyclopentane
Tetrahydronaphthalene
Cumene
(diglyme)
Methyl isobutyl ketone
Vinyl ethers
Cyclohexanol
Dioxanes
4-Methyl-2-pentanol
Other secondary alcohols
2-Cyclohexen-1-ol
Ethylene glycol dimethyl ether
2-Pentanol
Cyclohexene (glyme)
4-Penten-1-ol
Decahydronaphthalene
4-Heptanol
1-Phenylethanol


C. Chemicals that may autopolymerize as a result of peroxide accumulation


Acrylic acid b
Chlorotrifluoroethylene
Vinyl acetate
Vinyladiene chloride
Acrylonitrile b
Methyl methacrylate b
Vinylacetylene
Butadiene c
Styrene Vinyl chloride
Chloroprene c
Tetrafluoroethylene c
Vinylpyridine


D. Chemicals that may form peroxides but cannot clearly be placed in sections A - C.

Acrolein
tert--Butyl ethyl ether
1,3-Dioxepane d
4-Methyl-2-pentanone
Allyl ether d
tert-Butyl methyl ether
Di(1-propynyl)ether f
n-Methylphenetole
Allyl ethyl ether
n-Butyl phenyl ether
Di(2-propynyl)ether
2-Methyl tetrahydrofuran
Allyl phenyl ether
n-Butyl vinyl ether
Di-n-propoxymethane d
3-Methoxy-1-butyl acetate
p-(n-Amyloxy)benzoyl chloride
Chloroacetaldehyde
diethylacetal d
1,2-Epoxy-3-isopropoxypropane d
2-Methoxy-ethanol
n-Amyl ether
2-Chlorobutadiene
1,2-Epoxy-3-phenoxypropane
3-Methoxyethyl acetate
Benzyl n-butyl ether d
1-(2-Chloroethoxy)-2-phenoxyethane
p-Ethoxy acethophenone
2-Methoxyethyl vinyl ether
Benxyl ether d
Chloroethylene
1-(2-Ethoxyethoxy)-ethyl acetate
Methonxy-1,3,5,7-cyclooctatetraene
Benzyl ethyl ether d
Chloromethyl methyl ether e
2-Ethoxyethyl acetate
B-Methoxy-propionitrile
Benzyl methyl ether
B-Chlorophenetole
(2-Ethoxyethyl)-o-benzoyl benzoate
m-Nitro-phenetole
Benzyl 1-napthyl ether d
o-Chlorophenetole
1-Ethoxynaphthalene
1-Octene
1,2-Bis(2-chloroethoxy) -ethane
p-Chlorophenetole
o,p-Ethoxyphenyl isocyanate
Oxybis(2-ethyl acetate)
Bis(2 ethoxyethyl)ether
Cyclooctene d
1-Ethoxy-2-propyne
Oxybis(2-ethyl benzoate)
Bis(2(methoxyethoxy)-ethyl) ether
Cyclopropyl methyl ether
3-Ethoxyopropionitrile
B,B-oxydi-propionitrile
Bis(2-chloroethyl) ether
Diallyl ether d
2-Ethyl acrylaldehyde oxime
1-Pentene
Bis(2-ethoxyethyl) adipate
p-Di-n-butoxybenzene 2-Ethylbutanol
Phenoxyacetyl chloride
Bis(2-ethoxyethyl) phthalate
1,2-Dibenzyloxyethane d
Ethyl B-ethoxy-propionate
a-Phenoxy-propionyl chloride
Bis(2-methoxyethyl) carbonate
p-Dibenzyloxybenzene d
2-Ethylhexanal
Phenyl o-propyl ether
Bis(2-methoxyethyl) ether
1,2-Dichloroethyl ethyl ether
Ethyl vinyl ether
p-Phenylphenetone
Bis(2-methoxyethyl) phthalate
2,4-Dichlorophenetole
Furan
n-Propyl ether
Bis(2-methoxymethyl) adipate
Diethoxymethane d
2,5-Hexadiyn-1-ol
n-Propyl isopropyl ether
Bis(2-n-butoxyethyl) phthalate
2,2-Diethoxypropane
4,5-Hexadien-2-yn-1-ol
Sodium 8,11,14-eicosa-tetraenoate
Bis(2-phenoxyethyl) ether
Diethyl ethoxymethylene-malonate
n-Hexyl ether
Sodium ethoxyacetylide f
Bis(4-chlorobutyl) ether
Diethyl fumarated
o,p-Iodophenetole Tetrahydropyran
Bis(chloromethyl) ether e
Diethyl acetal d
Isoamyl benzyl ether d
Triethylene glycol diacetate
2-Bromomethyl ethyl ether
Diethyketene f
Isoamyl ether d
Triethylene glycol dipropionate
B-Bromophenetole
m,o,p-diethoxybenzene
Isobutyl vinyl ether
1,3,3-Trimethoxy-propene d
o-Bromophenetole
1,2-Diethoxyethane
Isophorone d
1,1,2,3-Tetrachloro-1,3-butadiene
p-Bromophenetole
Dimethoxymethane d
B-Isopropoxy-propionitrile d
4-Vinyl cyclohexene
3-Bromopropyl phenyl ether
1,1-Dimethoxyethane d
Isopropyl 2,4,5-tri-chlorophenoxyacetate
Vinylene carbonate
1,3-Butadiyne
Dimethylketene f
Limonene
Vinylidene chloride d
Buten-3-yne
3,3-Dimethoxypropene
1,5-p-Methadiene
2,4-Dinitrophenetole
Methyl p-(n-amyloxy)benzoate


NOTES:

a When stored as a liquid monomer.

b Although these chemicals form peroxides, no explosions involving these monomers have been reported.

c When stored in liquid form, these chemicals form explosive levels of peroxides without concentration. They may also be stored as a gas in gas cylinders. When stored as a gas, these chemicals may autopolymerize as a result of peroxide accumulation.

d These chemicals easily form peroxides and should probably be considered under Part B.

e OSHA - regulated carcinogen.

f Extremely reactive and unstable compound.


References:


Prudent Practices in the Laboratory, National Research Council, 1995.

"Review of Safety Guidelines for Peroxidizable Organic Chemicals," Chemical Health and Safety, September/October 1996.

chromatographer1;
thank you for posting the long list.
It is really interesting to me because I find that any secondary alcohols and any alkenes can form peroxides though I know ether can