Ketonic decarboxylation

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Ketonic decarboxylation (also known as decarboxylative ketonization) is a type of organic reaction and a decarboxylation converting two equivalents of a carboxylic acid (R−C(=O)OH) to a symmetric ketone (R2C=O) by the application of heat. It can be thought of as a decarboxylative Claisen condensation of two identical molecules. Water and carbon dioxide are byproducts: [1]

Contents

2 RCO2H → R2CO + CO2 + H2O

Bases promote this reaction. The reaction mechanism is proposed to involve nucleophilic attack of the alpha-carbon of one acid group on the other carboxylic acid group, possibly as a concerted reaction with the decarboxylation. [1] The initial formation of an intermediate carbanion via decarboxylation of one of the acid groups prior to the nucleophilic attack is unlikely since the byproduct resulting from the carbanion's protonation by the acid has not been reported. [2] This reaction is different from oxidative decarboxylation, which proceeds through a radical mechanism and is characterised by a different product distribution in isotopic labeling experiments with two different carboxylic acids. With two different carboxylic acids, the reaction behaves poorly because of poor selectivity except when one of the acids (for example, a small, volatile one) is used in large excess.

Examples

The dry distillation of calcium acetate to give acetone was reported by Charles Friedel in 1858 [3] and until World War I ketonization was the premier commercial method for its production. [4]

Ketonic decarboxylation of propanoic acid over a manganese(II) oxide catalyst in a tube furnace affords 3-pentanone. [5]

5-Nonanone, which is potentially of interest as a diesel fuel, can be produced from valeric acid. [6] Stearone is prepared by heating magnesium stearate. [7]

Metal oxide catalysts

Dozens or more metal oxides have been investigated as catalysts for the decarboxylation. Early work focused on the oxides of calcium and thorium. [8] Of commercial interest are related ketonizations using cerium(IV) oxide and manganese dioxide on alumina as the catalysts. The synthesis of 4-heptanone illustrates the production of the metal carboxylate in situ. Iron powder and butyric acid are converted to iron butyrate. Pyrolysis of that salt gives the ketone. [9]

Intramolecular decarboxylations

The intramolecular version of ketonic decarboxylation is often called the Ružička large-ring synthesis (or Ružička cyclization), named for Lavoslav Ružička who developed the technique from prior methods that could synthesize small cyclic compounds from calcium salts of dicarboxylic acids. [10] It was the first synthesis to directly produce cyclic compounds with more than 8 members and was used by Ružička to produce macrocyclic molecules with up to 34 carbon atoms. One target for such reactions are the naturally occurring fragrances civetone and muscone. The method involved dry distillation of dibasic salts of a dicarboxylic acid, such as thorium, cerium, and yttrium salts, mixed with copper powder to improve heat transfer. This method was low-yielding for large ring sizes and was eventually supplanted by various methods using the high dilution principle. [11]

The Ruzicka large-ring synthesis Ruzicka-Cyclisierung.svg
The Ruzicka large-ring synthesis

A more conventional example of intramolecular ketonization is the conversion of adipic acid to cyclopentanone with barium hydroxide. [12]

Ketonization (other meaning)

Ketonization can also refer to the conversion of some enols to the ketone. Such a conversion is the reverse of enolization. [13]

Related Research Articles

<span class="mw-page-title-main">Carboxylic acid</span> Organic compound containing a –C(=O)OH group

In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group attached to an R-group. The general formula of a carboxylic acid is often written as R−COOH or R−CO2H, sometimes as R−C(O)OH with R referring to an organyl group, or hydrogen, or other groups. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion.

<span class="mw-page-title-main">Ketone</span> Organic compounds of the form >C=O

In organic chemistry, a ketone is an organic compound with the structure R−C(=O)−R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group −C(=O)−. The simplest ketone is acetone, with the formula (CH3)2CO. Many ketones are of great importance in biology and industry. Examples include many sugars (ketoses), many steroids, and the solvent acetone.

Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carboxylation, the addition of CO2 to a compound. Enzymes that catalyze decarboxylations are called decarboxylases or, the more formal term, carboxy-lyases (EC number 4.1.1).

<span class="mw-page-title-main">Hydrazone</span> Organic compounds - Hydrazones

Hydrazones are a class of organic compounds with the structure R1R2C=N−NH2. They are related to ketones and aldehydes by the replacement of the oxygen =O with the =N−NH2 functional group. They are formed usually by the action of hydrazine on ketones or aldehydes.

The Friedel–Crafts reactions are a set of reactions developed by Charles Friedel and James Crafts in 1877 to attach substituents to an aromatic ring. Friedel–Crafts reactions are of two main types: alkylation reactions and acylation reactions. Both proceed by electrophilic aromatic substitution.

In organic chemistry, a nitrile is any organic compound that has a −C≡N functional group. The name of the compound is composed of a base, which includes the carbon of the −C≡N, suffixed with "nitrile", so for example CH3CH2C≡N is called "propionitrile". The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, including methyl cyanoacrylate, used in super glue, and nitrile rubber, a nitrile-containing polymer used in latex-free laboratory and medical gloves. Nitrile rubber is also widely used as automotive and other seals since it is resistant to fuels and oils. Organic compounds containing multiple nitrile groups are known as cyanocarbons.

<span class="mw-page-title-main">Nitro compound</span> Organic compound containing an −NO₂ group

In organic chemistry, nitro compounds are organic compounds that contain one or more nitro functional groups. The nitro group is one of the most common explosophores used globally. The nitro group is also strongly electron-withdrawing. Because of this property, C−H bonds alpha (adjacent) to the nitro group can be acidic. For similar reasons, the presence of nitro groups in aromatic compounds retards electrophilic aromatic substitution but facilitates nucleophilic aromatic substitution. Nitro groups are rarely found in nature. They are almost invariably produced by nitration reactions starting with nitric acid.

In organic chemistry, ozonolysis is an organic reaction where the unsaturated bonds are cleaved with ozone. Multiple carbon–carbon bond are replaced by carbonyl groups, such as aldehydes, ketones, and carboxylic acids. The reaction is predominantly applied to alkenes, but alkynes and azo compounds are also susceptible to cleavage. The outcome of the reaction depends on the type of multiple bond being oxidized and the work-up conditions.

In organic chemistry, the Knoevenagel condensation reaction is a type of chemical reaction named after German chemist Emil Knoevenagel. It is a modification of the aldol condensation.

<i>N</i>,<i>N</i>-Dicyclohexylcarbodiimide Chemical compound

N,N′-Dicyclohexylcarbodiimide (DCC or DCCD) is an organic compound with the chemical formula (C6H11N)2C. It is a waxy white solid with a sweet odor. Its primary use is to couple amino acids during artificial peptide synthesis. The low melting point of this material allows it to be melted for easy handling. It is highly soluble in dichloromethane, tetrahydrofuran, acetonitrile and dimethylformamide, but insoluble in water.

The Dakin–West reaction is a chemical reaction that transforms an amino-acid into a keto-amide using an acid anhydride and a base, typically pyridine. It is named for Henry Drysdale Dakin and Randolph West. In 2016 Schreiner and coworkers reported the first asymmetric variant of this reaction employing short oligopeptides as catalysts.

<span class="mw-page-title-main">Favorskii rearrangement</span> Chemical reaction

The Favorskii rearrangement is principally a rearrangement of cyclopropanones and α-halo ketones that leads to carboxylic acid derivatives. In the case of cyclic α-halo ketones, the Favorskii rearrangement constitutes a ring contraction. This rearrangement takes place in the presence of a base, sometimes hydroxide, to yield a carboxylic acid, but usually either an alkoxide base or an amine to yield an ester or an amide, respectively. α,α'-Dihaloketones eliminate HX under the reaction conditions to give α,β-unsaturated carbonyl compounds. Note that trihalomethyl ketone substrates will result in haloform and carboxylate formation via the haloform reaction instead.

The Hunsdiecker reaction is a name reaction in organic chemistry whereby silver salts of carboxylic acids react with a halogen to produce an organic halide. It is an example of both a decarboxylation and a halogenation reaction as the product has one fewer carbon atoms than the starting material and a halogen atom is introduced its place. A catalytic approach has been developed.

<span class="mw-page-title-main">Lead(IV) acetate</span> Organometallic compound (Pb(C2H3O2)4)

Lead(IV) acetate or lead tetraacetate is an metalorganic compound with chemical formula Pb(C2H3O2)4. It is a colorless solid that is soluble in nonpolar, organic solvents, indicating that it is not a salt. It is degraded by moisture and is typically stored with additional acetic acid. The compound is used in organic synthesis.

In organic chemistry, the Nef reaction is an organic reaction describing the acid hydrolysis of a salt of a primary or secondary nitroalkane to an aldehyde or a ketone and nitrous oxide. The reaction has been the subject of several literature reviews.

Alcohol oxidation is a collection of oxidation reactions in organic chemistry that convert alcohols to aldehydes, ketones, carboxylic acids, and esters. The reaction mainly applies to primary and secondary alcohols. Secondary alcohols form ketones, while primary alcohols form aldehydes or carboxylic acids.

<span class="mw-page-title-main">Jones oxidation</span> Oxidation of alcohol

The Jones oxidation is an organic reaction for the oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. It is named after its discoverer, Sir Ewart Jones. The reaction was an early method for the oxidation of alcohols. Its use has subsided because milder, more selective reagents have been developed, e.g. Collins reagent.

Decarboxylative cross coupling reactions are chemical reactions in which a carboxylic acid is reacted with an organic halide to form a new carbon-carbon bond, concomitant with loss of CO2. Aryl and alkyl halides participate. Metal catalyst, base, and oxidant are required.

<span class="mw-page-title-main">Cyclobutanone</span> Chemical compound

Cyclobutanone is an organic compound with molecular formula (CH2)3CO. It is a four-membered cyclic ketone (cycloalkanone). It is a colorless volatile liquid at room temperature. Since cyclopropanone is highly sensitive, cyclobutanone is the smallest easily handled cyclic ketone.

α,β-Unsaturated carbonyl compound Functional group of organic compounds

α,β-Unsaturated carbonyl compounds are organic compounds with the general structure (O=CR)−Cα=Cβ−R. Such compounds include enones and enals, but also carboxylic acids and the corresponding esters and amides. In these compounds, the carbonyl group is conjugated with an alkene. Unlike the case for carbonyls without a flanking alkene group, α,β-unsaturated carbonyl compounds are susceptible to attack by nucleophiles at the β-carbon. This pattern of reactivity is called vinylogous. Examples of unsaturated carbonyls are acrolein (propenal), mesityl oxide, acrylic acid, and maleic acid. Unsaturated carbonyls can be prepared in the laboratory in an aldol reaction and in the Perkin reaction.

References

  1. 1 2 Pham, Tu N.; Sooknoi, Tawan; Crossley, Steven P.; Resasco, Daniel E. (2013). "Ketonization of Carboxylic Acids: Mechanisms, Catalysts, and Implications for Biomass Conversion". ACS Catalysis. 3 (11): 2456–2473. doi:10.1021/cs400501h.
  2. Renz, M (2005). "Ketonization of Carboxylic Acids by Decarboxylation: Mechanism and Scope" (PDF). Eur. J. Org. Chem. 2005 (6): 979–988. doi:10.1002/ejoc.200400546 via The Vespiary.
  3. Friedel, C. (1858). "Ueber s. G. gemischte Acetone". Annalen der Chemie und Pharmacie. 108: 122–125. doi:10.1002/jlac.18581080124.
  4. Squibb, E. R. (1895). "Improvement in the Manufacture of Acetone.1". Journal of the American Chemical Society. 17 (3): 187–201. doi:10.1021/ja02158a004.
  5. Furniss, Brian; Hannaford, Antony; Smith, Peter; Tatchell, Austin (1996). Vogel's Textbook of Practical Organic Chemistry 5th Ed. London: Longman Science & Technical. p.  613. ISBN   9780582462366.
  6. Pileidis, Filoklis D.; Titirici, Maria-Magdalena (2016). "Levulinic Acid Biorefineries: New Challenges for Efficient Utilization of Biomass". ChemSusChem. 9 (6): 562–582. Bibcode:2016ChSCh...9..562P. doi:10.1002/cssc.201501405. PMID   26847212.
  7. A. G. Dobson and H. H. Hatt (1953). "Stearone". Organic Syntheses. 33: 84. doi:10.15227/orgsyn.033.0084.
  8. Kumar, Rawesh; Enjamuri, Nagasuresh; Shah, Sneha; Al-Fatesh, Ahmed Sadeq; Bravo-Suárez, Juan J.; Chowdhury, Biswajit (2018). "Ketonization of oxygenated hydrocarbons on metal oxide based catalysts". Catalysis Today. 302: 16–49. doi:10.1016/j.cattod.2017.09.044.
  9. Davis, Robert; Granito, Charles; Schultz, Harry P. (1967). "4-Heptanone". Organic Syntheses. 47: 75. doi:10.15227/orgsyn.047.0075.
  10. L. Ruzicka; M. Stoll; H. Schinz (1926). "Zur Kenntnis des Kohlenstoffringes II. Synthese der carbocyclischen Ketone vom Zehner- bis zum Achtzehnerring". Helvetica Chimica Acta . 9 (1): 249–264. doi:10.1002/hlca.19260090130.
  11. Agrawal, O. P. (2009). Agrawal, Shipra (ed.). Organic Chemistry – Reactions and Reagents (46th ed.) (46 ed.). India: Krishna Prakashan Media. pp. 237–246. ISBN   978-81-87224-65-5.
  12. Thorpe, J. F.; Kon, G. A. R. (1925). "Cyclopentanone". Org. Synth. 5: 37. doi:10.15227/orgsyn.005.0037.
  13. Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 794, ISBN   978-0-471-72091-1