108-10-1

Usage

Uses

4-Methyl-2-pentanone is used as a solvent for gums, resins, nitrocellulose, cellulose ethers, and various fats, oils, and waxes. It is also used in the production of paints, glues, and cleaning agents.
Used in Paint and Coatings Industry:
4-Methyl-2-pentanone is used as a solvent for paints, lacquers, and varnishes, providing a smooth application and enhancing the drying process.
Used in Plastic and Petrol Industries:
In the plastic and petrol industries, 4-Methyl-2-pentanone is utilized for its solvent properties, aiding in the manufacturing and processing of these materials.
Used in Flavor and Fragrance Industry:
4-Methyl-2-pentanone is used as a synthetic flavoring agent in some varieties of rum, candy, and cheese, thanks to its sweet, ethereal, banana, and fruity taste with dairy nuances.
Used in Extraction Processes:
As an organic solvent, 4-Methyl-2-pentanone is employed in extraction processes to separate and isolate various compounds.
Used as a Denaturant:
4-Methyl-2-pentanone is used as a denaturant for rubbing alcohol, modifying its properties to make it unsuitable for consumption.
In addition to these applications, 4-Methyl-2-pentanone can be found in various natural sources such as orange and lemon juice, grape, vinegar, baked potato, papaya, ginger, wheat bread, cheeses, milk, cooked egg, roast chicken, cooked beef, lamb fat, pork liver, hop oil, beer, cognac, coffee, tea, plumcot, plum brandy, mushroom, trassi, sesame seed, buckwheat, wort, elder flower, Bourbon vanilla, clary and red sage, crab, clam, and Chinese quince.

Preparation

By hydrogenation of mesityl oxide over Ni at 160 to 190°C; also by oxidation of methyl isobutyl carbinol.

Production Methods

Methyl isobutyl ketone can be manufactured by two processes . The first is a mixed ketone process where MiBK, diisobutyl ketone, and acetone are coproduced in a single reaction using isopropanol as a starting material. The second method is used to produce the majority of MiBK and involves a three-step reaction sequence in which diacetone alcohol and mesityl oxide are formed as intermediates.

Synthesis Reference(s)

Journal of the American Chemical Society, 100, p. 5437, 1978 DOI: 10.1021/ja00485a031Tetrahedron Letters, 36, p. 2285, 1995 DOI: 10.1016/0040-4039(95)00191-ETetrahedron, 37, p. 3073, 1981 DOI: 10.1016/S0040-4020(01)98839-8

Air & Water Reactions

Highly flammable. 4-Methyl-2-pentanone is sensitive to air (may form explosive peroxides). Slightly soluble in water.

Reactivity Profile

4-Methyl-2-pentanone is incompatible with caustic soda and other strong alkalis, hydrochloric acid, sulfuric acid and other strong inorganic acids, amines and oxidizing agents such as hydrogen peroxide, nitric acid, perchloric acid and chromium trioxide. 4-Methyl-2-pentanone reacts violently with potassium tert-butoxide. 4-Methyl-2-pentanone reacts vigorously with reducing materials. .

Hazard

Flammable, dangerous fire risk, explosivelimits in air 1.4–7.5%. Avoid ingestion and inhala-tion. Upper respiratory tract irritant, dizziness, andheadache. Possible carcinogen.

Health Hazard

Vapor causes irritation of eyes and nose; high concentrations cause anesthesia and depression. Liquid dries out skin and may cause dermatitis; irritates eyes but does not injure them.

Health Hazard

MIBK exhibits low to moderate toxicity.It is more toxic than acetone. Exposureto 200 ppm can cause irritation of theeyes, mucous membranes, and skin. Prolonged skin contact can leach out fat fromthe skin. Exposure to high concentrationscan cause nausea, headache, and narcosis. Animal studies indicate that this compound could probably cause kidney damage,with symptoms of a heavier kidney, higherkidney-to-body weight ratio, and tubularnecrosis. An increase in liver weight wasnoted, too, associated with its exposure inanimal subjects. In male rats the effect wasobserved at 2000 ppm on 2 weeks’ exposure(6 hours/day) (Phillips et al. 1987). Otherthan for the male rat kidney effect, the levelsup to 1000 ppm for 14 weeks had no significant toxicological effect. In another study,exposure to 3000 ppm in rats and mice wasfound to cause increased liver and kidneyweights, decrease in food consumption, incidence of dead fetuses, and reduced fetal bodyweight (Tyl et al. 1987).Ingestion of MIBK can result in narcosis and coma. A genetic toxicology studyof MIBK showed a negative response inthe bacterial mutation assays and the yeastmitotic gene conversion assay (Brooks et al.1988).LD50 value, oral (rat): 2080 mg/kgLD50 value, intraperitoneal (rat): 400 mg/kg.

Flammability and Explosibility

Highlyflammable

Chemical Reactivity

Reactivity with Water No reaction; Reactivity with Common Materials: No reaction; Stability During Transport: Stable; Neutralizing Agents for Acids and Caustics: Not pertinent; Polymerization: Not pertinent; Inhibitor of Polymerization: Not pertinent.

Potential Exposure

MIBK is used as a solvent; a denaturant; and as an extractant; in the manufacture of methyl amyl alcohol; as a solvent in paints, varnishes, and lacquers; as an alcohol denaturant; as a solvent in uranium extraction from fission products.

Carcinogenicity

The National Toxicology Program conducted cancer bioassays by exposing groups of 50 male and 50 female F344 rats and B6C3F1 mice to MiBK vapor at 0, 450, 900, or 1800 ppm 6h/day, 5 days/ week for 2 years. Survival and body weight gain were decreased in male rats at 1800 ppm. Body weight gain was also decreased in male rats at 900 and in female mice at 1800ppm. A higher incidence of mineralization of the renal papilla was observed in male rats at all MiBK exposure levels. Chronic progressive nephropathy (CPN) and the incidences of adenoma and adenoma or carcinoma (combined) were increased for the male 1800 ppm exposure group. The severity of CPN and renal tubular hyperplasia was increased in all male rat exposure groups. An uncertain increase in mononuclear cell leukemia, adrenal medulla hyperplasia, and a positive trend for increases in benign or malignant pheochromocytomas (combined) were reported for the 1800 ppm male group. The NTP considered that there was some evidence of carcinogenic activity in male rats based on increased incidences of renal tubule neoplasms. None of the rodent bioassay results were considered clear evidence of carcinogenicity by NTP.

Environmental fate

Biological. Bridié et al. (1979) reported BOD and COD values of 2.06 and 2.16 g/g using filtered effluent from a biological sanitary waste treatment plant. These values were determined using a standard dilution method at 20 °C and stirred for a period of 5 d. Heukelekian and Rand (1955) reported a 5-d BOD value of 1.51 g/g which is 55.5% of the ThOD value of 2.72 g/g. Photolytic. When synthetic air containing gaseous nitrous acid and 4-methyl-2-pentanone was exposed to artificial sunlight (λ = 300–450 nm), photooxidation products identified were acetone, peroxyacetal nitrate, and methyl nitrate (Cox et al., 1980). In a subsequent experiment, the OHinitiated photooxidation of 4-methyl-2-pentanone in a smog chamber produced acetone (90% yield) and peroxyacetal nitrate (Cox et al., 1981). Irradiation at 3130 ? resulted in the formation of acetone, propyldiene, and free radicals (Calvert and Pitts, 1966). Second-order photooxidation rate constants for the reaction of 4-methyl-2-butanone and OH radicals in the atmosphere are 1.4 x 10-10, 1.42 x 10-10, and 1.32 x 10-10 cm3/molecule?sec at 295, 299, and 300 K, respectively (Atkinson, 1985). The atmospheric lifetime was estimated to be 1–5 d (Kelly et al., 1994). Photolytic. Cox et al. (1980) reported a rate constant of 1.24 x 10-11 cm3/molecule?sec for the reaction of gaseous 4-methyl-2-pentanone with OH radicals based on a value of 8 x 10-12 cm3/molecule?sec for the reaction of ethylene with OH radicals. Chemical/Physical. 4-Methyl-2-pentanone will not hydrolyze in water because it does not contain a hydrolyzable functional group (Kollig, 1993).

Shipping

UN1245 Methyl isobutyl ketone, Hazard Class: 3; Labels: 3-Flammable liquid.

Purification Methods

Reflux the ketone with a little KMnO4, wash it with aqueous NaHCO3, dry with CaSO4 and distil it. Acidic impurities are removed by passage through a small column of activated alumina. [Beilstein 1 IV 3305.]

Incompatibilities

Able to form unstable and explosive peroxides on contact with air. Reacts violently with strong oxidizers, potassium tert-butoxide; strong acids; aliphatic amines; reducing agents

Waste Disposal

Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform to EPA regulations governing storage, transportation, treatment, and waste disposal. Incineration.

InChI:InChI=1/C6H12O/c1-5(2)4-6(3)7/h5H,4H2,1-3H3

Upstream product

• 186581-53-3 diazomethane 
• 590-86-3 isovaleraldehyde 
• 67-56-1 methanol 
• 19860-68-5 2-methyl-6-methylene-7-octene-4-one 
• 108-11-2 Methyl isobutyl carbinol 
• 56-23-5 tetrachloromethane 
• 3002-23-1 6-methylheptan-2,4-dione 
• 917-64-6 methyl magnesium iodide 
• 625-28-5 Isovaleronitrile 
• 141-79-7 4-methyl-pent-3-en-2-one 
• 64-17-5 ethanol 
• 123-51-3 i-Amyl alcohol 
• 127-19-5 N,N-dimethyl acetamide 
• 920-36-5 (2-methylpropyl)lithium 

Downstream Products

• 56750-95-9 1t-benzo[1,3]dioxol-5-yl-5-methyl-hex-1-en-3-one 
• 3002-23-1 6-methylheptan-2,4-dione 
• 1540-38-1 3-(1-methylethyl)pentane-2,4-dione 
• 76216-40-5 3-isopropyl-pentane-2,4-dione (E)-enol tautomer 
• 7338-49-0 5-(1,3-dimethyl-butylidene)-cyclopenta-1,3-diene 
• 43213-34-9 cis-2,6-diphenyl-trans-3-isopropylpiperidin-4-one 
• 42180-20-1 cis-2,6-diphenyl-trans-3-isopropyl-N-methylpiperidin-4-one 
• 2892-18-4 5-methyl-1-phenyl-hex-1-en-3-one 
• 18346-82-2 (+/-)-2r-isopropyl-4c-isovaleryl-3t,5c-diphenyl-cyclohexanone 
• 82297-68-5 (E)-1-(4-methoxyphenyl)-5-methylhex-1-en-3-one 
• 54596-70-2 2-(1,3-dimethyl-butylamino)-ethanol 
• 2035-08-7 4-methyl-2-pentanone ethylene acetal 
• 98489-37-3 4-isobutyl-pyrimidine 
• 6668-06-0 2-cyano-3,5-dimethyl-hex-2-enoic acid methyl ester 

Relevant academic research and scientific papers

Palladium catalyzed mild reduction of α,β-unsaturated compounds by triethylsilane

The palladium(II) chloride/triethylsilane system has been successfully applied for the selective hydrogenation of the carbon-carbon double bond of α,β-unsaturated ketones to yield the corresponding saturated carbonyl compounds. The reaction takes place under mild conditions and affords high yields.

Multifunctional catalysis by Pd-polyoxometalate: One-step conversion of acetone to methyl isobutyl ketone

Pd metal supported on Cs2.5H0.5PW12O 40 is an efficient bifunctional catalyst for the one-step conversion of acetone to methyl isobutyl ketone in gas and liquid phase. The Royal Society of Chemistry 2006.

Use of reductive properties of iodotrichlorosilane II: Chemoselective reduction of α,β-unsaturated ketones and nitriles

A new synthetic procedure for the selective reduction of α,β-unsaturated ketones and nitriles, using iodotrichlorosilane (ITCS generated in situ from SiCl4-NaI) under mild conditions to produce the corresponding saturated ketone and nitrile compounds in quantitative yields, is described.

Selective deoximation using alumina supported potassium permanganate

Ketoximes are converted to the parent ketones in good yields when treated with potassium permanganate supported on neutral alumina (ASPP). An optimized procedure has been developed, the simple work-up minimizes loss of product and oximes have been selectively oxidized in the presence of alkenes.

Alkoxy radical isomerization products from the gas-phase OH radical- initiated reactions of 2,4-dimethyl-2-pentanol and 3,5-dimethyl-3-hexanol

The products of the gas-phase reactions of the OH radical with 2,4- dimethyl-2-pentanol and 3,5-dimethyl-3-hexanol in the presence of NO(x) have been determined at atmospheric pressure of air and 296 ± 2 K to assess the occurrence and importance of alkoxy radical isomerization. The products identified and quantified and their formation yields were as follows: from 2,4-dimethyl-2-pentanol: acetone, 0.92 ± 0.15; 2-methylpropanal, 0.209 ± 0.022; 4-methyl-2-2-pentanone, 0.046 ± 0.008; and 4-hydroxy-4-methyl-2- pentanone, 0.116 ± 0.018; from 3,5-dimethyl-3-hexanol: acetone, 0.120 ± 0.029; 2-butanone, 0.275 ± 0.021; 2-methylpropanal, 0.169 ± 0.016; 4- methyl-2-pentanone, 0.161 ± 0.012; and 4-hydroxy-4-methyl-2-pentanone, 0.250 ± 0.023. The observed formation of 4-hydroxy-4-methyl-2-pentanone provides conclusive evidence for the occurrence of isomerization of the alkoxy radicals (CH3)2C(OH)CH2C(O)(CH3)2 and CH3CH2C(CH3)(OH)CH2C(O)(CH3)2 via 1,5-H shifts. The reaction mechanisms are discussed, and isomerization rate constants for 1,5-H-atom abstraction from the -CH3 and -CH2- groups in the RCH2C(CH3)(OH)- CH2C(O)(CH3)2 alkoxy radicals (R = H and CH3) are derived.

Ethanolic or aqueous formic acid (1:1) - A new efficient reagent for the regeneration of ketones from phenylhydrazones

50% Ethanolic or aqueous formic acid has been found to be extremely efficacious for the regeneration of aliphatic and aromatic ketones from phenylhydrazones.

Variable regiochemistry in the stoichiometric and catalytic hydroamination of alkynes by imidozirconium complexes caused by an unusual dependence of the rate law on alkyne structure and temperature

We have investigated the regiochemistry of the stoichiometric and catalytic hydroamination of disubstituted alkynes by imidozirconium complexes. The addition of alkynes to Cp2Zr=NR occurred regioselectively to give metallacycles 2, with the larger alkyne substituent RL located α to the metal center. Hydrolysis of the metallacycles then gave enamines and their tautomeric imines which were the net result of anti-Markovnikov addition to the alkyne. The size of the R group on the imido ligand and the size of the alkyne were influential in determining the degree of regioselectivity. By utilizing Cp2(THF)Zr=NR to generate Cp2Zr=NR at room temperature and Cp2Zr(R′)(NHR) to generate Cp2Zr=NR at high temperature, it was determined that the thermodynamic and kinetic regioselectivities were nearly identical for dialkylacetylenes. In contrast, for 1-phenylpropyne, the thermodynamic regioselectivity was found to be greater than the kinetic regioselectivity. The regioselectivity was found to be invariant from -6 to 45°C in the addition of both 4-methyl-2-pentyne and 2-hexyne to Cp2(THF)Zr=NAr. However, a significant erosion of regioselectivity was observed when 2-hexyne and 4-methyl-2-pentyne were catalytically hydroaminated by Cp2Zr(NHAr)2 at 120°C. A kinetic study of the catalytic reaction suggested that the reason for this erosion was that the protonation step in the catalytic cycle (k3[amine]) was slower than the cycloreversion of the stereoisomeric metallacycles to alkyne and Cp2Zr=NAr (k-2) (the step that leads to regioequilibration). Because the protonation is selective for the metallacycle in which the smaller substituent is located at the position adjacent to the metal center, it counters the regioselectivity of the cycloaddition. This was an unexpected result because (1) an earlier study showed that k3 [amine] was larger than k-2 for the addition of diphenylacetylene to Cp2Zr=NR at both 25°C and the catalytic reaction temperature (95°C in this case) and (2) in the present work, it was demonstrated that k3 [amine] was also larger than k-2 for dialkylacetylenes at 25°C. It was concluded that the relative magnitudes of the rate constants k3 (protonation) and k-2 (reversion) must vary with temperature more dramatically in the dialkylacetylene + Cp2Zr=NR reaction than in the diarylacetylene + Cp2Zr=NR reaction. This was confirmed by direct competition experiments carried out at 25, 60, and 100°C. We believe that the cycloreversion step k-2 is characterized by both a larger ΔH? and a larger ΔS? than protonation because the former is a unimolecular and the latter a bimolecular reaction.

Dehydration of 4-methylpentan-2-ol over lanthanum and cerium oxides

Lanthanum and cerium oxides have been tested for the title reaction at 623 K and atmospheric pressure in a flow reactor. Lanthanum oxide (prepared from the corresponding nitrate) gives mainly 4-methylpent-1-ene (80% of the products). Similar results are observed with cerium oxide obtained from the corresponding hydroxide, whereas cerium oxide prepared from nitrate is less selective towards alk-1-enes. In addition to dehydration, dehydrogenation to 4-methylpentan-2-one is also observed to a limited extent for all the catalysts. Information on the acid-base properties of the samples was obtained by adsorption microcalorimetry of ammonia and carbon dioxide and correlated to reaction selectivities. Possible changes in the oxidation state of cerium ions due to the reaction atmosphere are considered. The present results are compared with former data for zirconia catalysts. Modification of cerium oxide via immersion in NaOH solution does not appear to be useful for improving alk-1-ene selectivity.

The mechanism and kinetics of methyl isobutyl ketone synthesis from acetone over ion-exchanged hydroxyapatite

The synthesis of methyl isobutyl ketone (MIBK) can be carried out by the condensation of acetone in the presence of hydrogen over a supported metal catalyst. Previous studies have shown that hydroxyapatite is an excellent catalyst for condensation reactions. The present investigation was undertaken in order to elucidate the reaction mechanism and site requirements for acetone coupling to MIBK over a physical mixture of hydroxyapatite and Pd/SiO2. The reaction is found to proceed by consecutive aldol addition to form diacetone alcohol (DAA), dehydration of DAA to mesityl oxide (MO), and hydrogenation of MO to MIBK. The products formed by feeding DAA and MO reveal that aldol addition of acetone is rapid and reversible, and that the subsequent dehydration of DAA is rate-limiting. Pyridine and CO2 titration show that aldol dehydration occurs over basic sites via an E1cB mechanism. A series of cation-substituted hydroxyapatite samples were prepared by ion-exchange to further investigate the role of acid-base strength on catalyst performance. Characterization of these samples by PXRD, BET, ICP-OES, XPS, CO2-TPD, and Raman spectroscopy demonstrated that the exchange procedure used does not affect the bulk properties of hydroxyapatite. DFT calculations reveal that in addition to affecting the Lewis acidity/basicity of the support, the size of the cation plays a significant role in the chemistry: cations that are too large (Ba2+) or too small (Mg2+) adversely affect reaction rates due to excessive stabilization of intermediate species. Strontium-exchanged hydroxyapatite was found to be the most active catalyst because it promoted α-hydrogen abstraction and C–O bond cleavage of DAA efficiently.

Effect of metal modification of titania and hydrogen co-feeding on the reaction pathways and catalytic stability in the acetone aldol condensation

A stable performance of TiO2 catalysts for gas-phase acetone aldol condensation was observed when reduced metals were added (Pt or Ni, 1.5 wt%) and the reactions were conducted in presence of hydrogen. In both cases, the resulting metal-loaded catalysts are stable for 10 h, whereas continuous deactivation is observed for the parent TiO2 catalyst (573 K). Both the activation of the H2 molecule by metal nanoparticles and the change of the catalytic surface by metal insertion (in the case of Ni-loaded catalyst) enable suppressing oligomerization (by hindering enolates formation) and the strong adsorption of intermediates (by decreasing the concentration of high-strength acid-basic active sites), respectively. More interestingly, these metals allow to tune the selectivity of the reaction. Indeed, the Ni-loaded titania catalyst is highly selective for the synthesis of α,β-unsaturated ketones (selectivity to unsaturated C6 and C9 species >98%, at ～12% acetone conversion), whereas the Pt-loaded one is highly selective to the formation of saturated C6 and C9 ketones (MIBK and DIBK, with selectivities >95% at ～42% acetone conversion). The catalytic activity and stability of the two materials (Ni/TiO2 and Pt/TiO2) in both absence and presence of H2 are compared between them and with those of the parent TiO2. The results obtained by the reaction gas-phase analysis are supplemented through different solid characterization techniques (i.e., CO2-TPD and NH3-TPD, HRTEM, XPS, TPO, and DRIFTS).