Koch reaction
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The Koch reaction is an organic reaction for the synthesis of tertiary carboxylic acids from alcohols or
alkenes In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
. The
reaction Reaction may refer to a process or to a response to an action, event, or exposure: Physics and chemistry *Chemical reaction *Nuclear reaction * Reaction (physics), as defined by Newton's third law *Chain reaction (disambiguation). Biology and m ...
is a strongly acid-
catalyzed Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
carbonylation Carbonylation refers to reactions that introduce carbon monoxide into organic and inorganic substrates. Carbon monoxide is abundantly available and conveniently reactive, so it is widely used as a reactant in industrial chemistry. The term carbony ...
using
carbon monoxide Carbon monoxide (chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simple ...
, and typically occurs at high pressures ranging from 50 to 5,000 k Pa, often requiring temperatures several hundred degrees higher than room temperature. Generally the reaction is conducted with strong mineral acids such as sulfuric acid, HF or BF3. Large scale operations for the
fine chemical In chemistry, fine chemicals are complex, single, pure chemical substances, produced in limited quantities in multipurpose plants by multistep batch chemical or biotechnological processes. They are described by exacting specifications, used f ...
industry produce almost 150,000 tonnes of Koch acids and their derivatives annuallyWeissermel, K., Jargen-Arpe, H. In "Syntheses involving carbon monoxide", ''Industrial Organic Chemistry''; VCH Publishers: New York, NY; pp. 141–145. () but also generate a great deal of waste, motivating ongoing attempts to use metal, solid acid, and other novel
catalysts Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
to enable the use of milder reaction conditions. Formic acid, which readily decomposes to carbon monoxide in the presence of acids or relatively low heat, is often used instead of carbon monoxide directly; this procedure was developed shortly after the Koch reaction and is more commonly referred to as the Koch–Haaf reaction. This variation allows for reactions at nearly standard room temperature and pressure. Some commonly industrially produced Koch acids include
pivalic acid Pivalic acid is a carboxylic acid with a molecular formula of (CH3)3CCO2H. This colourless, odiferous organic compound is solid at room temperature. A common abbreviation for the pivalyl or pivaloyl group (''t''-BuC(O)) is Piv and for pivalic acid ...
, 2,2-dimethylbutyric acid and 2,2-dimethylpentanoic acid.


Mechanism

When standard acid catalysts such as sulfuric acid or a mix of BF3 and HF are used, the mechanism begins by
protonation In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid ...
of the
alkene In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
, followed by carbon monoxide attack of the resulting carbocation. The subsequent
acylium In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC n ...
cation is then
hydrolysed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...
to the tertiary carboxylic acid. If the substrate is an alcohol, it is protonated and subsequently eliminated, generating a carbocation that is converted to an
acylium In chemistry, an acyl group is a moiety derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids. It contains a double-bonded oxygen atom and an alkyl group (). In organic chemistry, the acyl group (IUPAC n ...
cation by carbon monoxide and then
hydrolysed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...
. Tertiary carbocation formation is typically thermodynamically favored when considering hydride or alkyl shifts in the carbocation.


Catalyst usage and variations

Industrial large scale application of the Koch reaction using strong mineral acids is complicated by equipment
corrosion Corrosion is a natural process that converts a refined metal into a more chemically stable oxide. It is the gradual deterioration of materials (usually a metal) by chemical or electrochemical reaction with their environment. Corrosion engi ...
, separation procedures for products and difficulty in managing large amounts of
waste Waste (or wastes) are unwanted or unusable materials. Waste is any substance discarded after primary use, or is worthless, defective and of no use. A by-product, by contrast is a joint product of relatively minor economic value. A waste prod ...
acid. Several acid
resins In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on natu ...
and acidic
ionic liquids An ionic liquid (IL) is a salt in the liquid state. In some contexts, the term has been restricted to salts whose melting point is below a specific temperature, such as . While ordinary liquids such as water and gasoline are predominantly made of ...
Qiao, K., Yokoyama, C. '' Cat. Comm.'' 2006, ''7'', 450–453. () have been investigated in order to discover if Koch acids can be synthesized in more mild environments. Although the use of acidic ionic liquids for the Koch reaction requires relatively high temperatures and pressures (8 MPa and 430 K in one 2006 study), acidic ionic solutions themselves can be reused with only a very slight decrease in yield, and the reactions can be carried out biphasically to ensure easy separation of products. A large number of transition metal
catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...
cations An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by con ...
have also been investigated for usage in Koch-like reactions: Cu(I), Au(I) and Pd(I) carbonyl cations catalysts dissolved in sulfuric acid can allow the reaction to progress at room temperature and atmospheric pressure. Usage of a Nickel tetracarbonyl catalyst with CO and water as a nucleophile is known as the Reppe carbonylation, and there are many variations on this type of metal-mediated carbonylation used in industry, particularly those used by
Monsanto The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best known product is Roundup, a glyphosate-based herbicide, developed in ...
and the
Cativa process The Cativa process is a method for the production of acetic acid by the carbonylation of methanol. The technology, which is similar to the Monsanto process, was developed by BP Chemicals and is under license by BP Plc. The process is based on an ...
es, which convert methanol to acetic acid using acid catalysts and carbon monoxide in the presence of metal
catalysts Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
.


Side reactions

Koch reactions can involve a large number of side products, although high yields are generally possible (Koch and Haaf reported yields of over 80% for several alcohols in their 1958 paper). Carbocation rearrangements,
ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be ...
ization (in case an alcohol is used as a substrate, instead of an alkene), and occasionally substrate CN+1 carboxylic acids are observed due to fragmentation and dimerization of carbon monoxide-derived carbenium ions, especially since each step of the reaction is reversible. Alkyl sulfuric acids are also known to be possible side products, but are usually eliminated by the excess sulfuric acid used.


Applications

Koch–Haaf-type reactions see extensive use in rational drug design as a convenient way to generate crucial tertiary carboxylic acids. Companies such as
Shell Shell may refer to: Architecture and design * Shell (structure), a thin structure ** Concrete shell, a thin shell of concrete, usually with no interior columns or exterior buttresses ** Thin-shell structure Science Biology * Seashell, a hard o ...
and ExxonMobil produce
pivalic acid Pivalic acid is a carboxylic acid with a molecular formula of (CH3)3CCO2H. This colourless, odiferous organic compound is solid at room temperature. A common abbreviation for the pivalyl or pivaloyl group (''t''-BuC(O)) is Piv and for pivalic acid ...
from
isobutene Isobutylene (or 2-methylpropene) is a hydrocarbon with the chemical formula . It is a four-carbon branched alkene (olefin), one of the four isomers of butylene. It is a colorless flammable gas, and is of considerable industrial value. Producti ...
using the Koch reaction, as well as several other branched carboxylic acids. However, Koch–Haaf reactions are also utilized for the interrogation of several other topics. As the reactants are found in different phases, the Koch reaction has been used to study reaction kinetics of gas–liquid–liquid systemsBecker, C. L., Engstrom, K. M., Kerdesky, F. A., Tolle, J. C., Wagaw, S. H., Wang, W. '' Org. Process Res. Dev.'', 2008, ''12'', 1114–18. () as well as query the use of solid acid resins and acidic ionic liquids in reducing hazardous by-product waste.


References

{{DEFAULTSORT:Koch Reaction Addition reactions Name reactions