Chemical Properties
tert-Butyl hydroperoxide (TBHP) is a water-white liquid
commonly commercially available as a 70% solution in
water; 80% solutions are also available. It is used to initiate
polymerization reactions and in organic syntheses to introduce peroxy groups into the molecule.
Uses
TBHP is an intermediate in the production of propylene
oxide and t-butyl alcohol from isobutane and propylene. It is
primarily used as an initiator and finishing catalyst in the
solution and emulsion polymerization methods for polystyrene
and polyacrylates. Other uses are for the polymerization
of vinyl chloride and vinyl acetate and as an oxidation
and sulfonation catalyst in bleaching and deodorizing operations.
It is a strong oxidant and reacts violently with
combustible and reducing materials, and metallic and sulfur
compounds.
Uses
tert-Butyl hydroperoxide is used as an initiator for radical polymerization and in various oxidation process such as sharpless epoxidation. It is involved in osmium catalyzed vicinal hydroxylation of olefins under alkaline conditions. Furthermore, it is used in catalytic asymmetric oxidation of sulfides to sulfoxides using binaphthol as a chiral auxiliary and in the oxidation of dibenzothiophenes. It plays an important role for the introduction of peroxy groups in organic synthesis.
Production Methods
TBHP is produced by the liquid-phase reaction of isobutane
and molecular oxygen or by mixing equimolar amounts of
t-butyl alcohol and 30–50% hydrogen peroxide. TBHP can
also be prepared from t-butyl alcohol and 30% hydrogen
peroxide in the presence of sulfuric acid or by oxidation of
tert-butylmagnesium chloride. The manufacturing process of
TBHP is in a closed system.
Description
Tert-butyl hydroperoxide is an alkyl hydroperoxide in which the alkyl group is tert-butyl. It is widely used in a variety of oxidation processes. It has a role as an antibacterial agent and an oxidising agent.
General Description
Watery odorless colorless liquid. Floats and mixes slowly with water.
Reactivity Profile
Most alkyl monohydroperoxides are liquid. The explosivity of the lower members (e.g., methyl hydroperoxide, or possibly, traces of the dialkyl peroxides) decreasing with increasing chain length and branching [Bretherick 2nd ed. 1979 p. 10]. Though relatively stable, explosions have been caused by distillation to dryness [Milas, JACS 1946, 68, 205] or attempted distillation at atmospheric pressure [Castrantas 1965 p. 15].
Health Hazard
tert-Butyl hydroperoxide is a strong irritant.Floyd and Stockinger (1958) observed thatdirect cutaneous application in rats did notcause immediate discomfort, but the delayedaction was severe. The symptoms were erythemaand edema within 2–3 days. Exposureto 500 mg in 24 hours produced asevere effect on rabbit skin, while a rinse of150 mg/min was severe to eyes.
It is moderately toxic; the effects aresomewhat similar to those of MEK peroxide.Symptoms from oral administration in ratswere weakness, shivering, and prostration.
LD
50 value, intraperitoneal (rats): 87 mg/kg
LD
50 value, oral (rats): 406 mg/kg.
Flammability and Explosibility
tert-Butyl hydroperoxide is a flammable liquid and a highly reactive oxidizing agent.
Pure TBHP is shock sensitive and may explode on heating. Carbon dioxide or dry
chemical extinguishers should be used for fires involving tert-butyl hydroperoxide.
Mechanism of action
The general mechanism of transition metal-catalyzed oxidative Mannich reactions of N, N-dialkyl anilines with tert-butyl hydroperoxide (TBHP) as the oxidant consists of a rate-determining single electron transfer (SET) that is uniform from 4-methoxy- to 4-cyano-N, N-dimethylanilines. The tert-butylperoxy radical is the major oxidant in the rate-determining SET step that is followed by competing backward SET and irreversible heterolytic cleavage of the carbon–hydrogen bond at the α-position to nitrogen. A second SET completes the conversion of N, N-dimethylaniline to an iminium ion that is subsequently trapped by the nucleophilic solvent or the oxidant prior to the formation of the Mannich adduct[1].
Tert-butyl hydroperoxide could induce oxidative stress in liver mitochondria at low concentrations. The damaging effect of low concentrations of tBHP in the course of pyruvate oxidation in isolated liver mitochondria is caused by the opening of the nonspecific Ca
2+-dependent cyclosporin A-sensitive pore in the inner mitochondrial membrane[2].
Safety Profile
Moderately toxic by
ingestion and inhalation. A severe skin and
eye irritant. Mutation data reported. At
highest dosage levels, symptoms noted were
severe depression, incoordmation, and
cyanosis. Death was due to respiratory
arrest. Very dangerous fire hazard when
exposed to heat or flame, or by spontaneous
chemical reaction such as with reducing
materials. Moderately explosive; may
explode during distillation. Violent reaction
with traces of acid. Concentrated solutions
may ignite spontaneously on contact with
molecular sieve. Mixtures with transition
metal salts may react vigorously and release
oxygen. Forms an unstable solution with
1,2-dichloroethane. To fight fire, use alcohol
foam, CO2, dry chemical. When heated to
decomposition it emits acrid smoke and
fumes.
Carcinogenicity
A study performed to evaluate
the carcinogenicity of TBHP found it was not carcinogenic
when applied to the skin of mice at 16.6% of the peroxide 6
times a week for 45 weeks. However, if its application was
preceded by 0.05 mg of 4-nitroquinoline-1-oxide as a 0.25%
solution in benzene applied 20 times over 7 weeks followed
by TBHP (16.6% in benzene), then malignant skin tumors
appeared between days 390 and 405 of the experiment .
This supports the theory that peroxides are not complete
carcinogens, but may act as promoters . The effects of
TBHP on promotable and nonpromotable mouse epidermal
cell culture lines were reported by Muehlematter et al. .
storage
tert-butyl hydroperoxide should be stored in the dark at room temperature
(do not refrigerate) separately from oxidizable compounds, flammable substances,
and acids. Reactions involving this substance should be carried out behind a safety
shield.
Toxicity evaluation
TBHP accelerates oxidation of glutathione and decreases the
metabolism of sodium hexobarbital in rat livers and is a strong
oxidation agent.
Incompatibilities
tert-Butyl hydroperoxide and concentrated aqueous solutions of TBHP react
violently with traces of acid and the salts of certain metals, including, in particular,
manganese, iron, and cobalt. Mixing anhydrous tert-butyl hydroperoxide with
organic and readily oxidized substances can cause ignition and explosion. TBHP can
initiate polymerization of certain olefins.
Waste Disposal
Excess tert-butyl hydroperoxide and waste material containing this substance should be placed in an
appropriate container, clearly labeled, and handled according to your institution's waste disposal guidelines.
References
[1] Maxim O, et al. Mechanistic Investigation of Oxidative Mannich Reaction with tert-Butyl Hydroperoxide. The Role of Transition Metal Salt. Journal of the American Chemical Society, 2013; 135: 1549–1557.
[2] Fedotcheva N, et al. Mechanism of induction of oxidative stress in liver mitochondria by low concentrations of tert-butyl hydroperoxide. Biochemistry (Moscow), 2013; 78: 75–79.
