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).
In organic chemistry
The term "decarboxylation" literally means removal of the COOH (carboxyl group) and its replacement with a hydrogen. The term relates the state of the reactant and product. Decarboxylation is one of the oldest organic reactions, since it often entails simple pyrolysis, and volatile products distilled from the reactor. Heating is required because the reaction is less favorable at low temperatures. Yields are highly sensitive to conditions. In retrosynthesis, decarboxylation reactions can be considered the opposite of homologation reactions, in that the chain length becomes one carbon shorter. Metals, especially copper compounds, are usually required. Such reactions proceed via the intermediacy of metal carboxylate complexes.
Decarboxylation of aryl carboxylates can generate the equivalent of the corresponding aryl anion, which in turn can undergo cross coupling reactions.
Alkanoic acids and their salts do not always undergo decarboxylation readily. Exceptions are the decarboxylation of beta-keto acids, α,β-unsaturated acids, and α-phenyl, α-nitro, and α-cyanoacids. Such reactions are accelerated due to the formation of a zwitterionic tautomer in which the carbonyl is protonated and the carboxyl group is deprotonated. Typically fatty acids do not decarboxylate readily. Reactivity of an acid towards decarboxylation depends upon stability of carbanion intermediate formed in above mechanism. Many reactions have been named after early workers in organic chemistry. The Barton decarboxylation, Kolbe electrolysis, Kochi reaction and Hunsdiecker reaction are radical reactions. The Krapcho decarboxylation is a related decarboxylation of an ester. In ketonic decarboxylation a carboxylic acid is converted to a ketone.
Hydrodecarboxylations involve the conversion of a carboxylic acid to the corresponding hydrocarbon. This is conceptually the same as the more general term "decarboxylation" as defined above except that it specifically requires that the carboxyl group is, as expected, replaced by a hydrogen. The reaction is especially common in conjunction with the malonic ester synthesis and Knoevenagel condensations. The reaction involves the conjugate base of the carboxyl group, a carboxylate ion, and an unsaturated receptor of electron density, such as a protonated carbonyl group. Where reactions entail heating the carboxylic acid with concentrated hydrochloric acid, such a direct route is impossible as it would produce protonated carbon dioxide. In these cases, the reaction is likely to occur by initial addition of water and a proton.
- tryptophan to tryptamine
- phenylalanine to phenylethylamine
- tyrosine to tyramine
- histidine to histamine
- serine to ethanolamine
- glutamic acid to GABA
- lysine to cadaverine
- arginine to agmatine
- ornithine to putrescine
- 5-HTP to serotonin
- L-DOPA to dopamine
Other decarboxylation reactions from the citric acid cycle include:
- pyruvate to acetyl-CoA (see pyruvate decarboxylation)
- oxalosuccinate to α-ketoglutarate
- α-ketoglutarate to succinyl-CoA.
Upon heating, Δ9-Tetrahydrocannabinolic acid decarboxylates to give the psychoactive compound Δ9-Tetrahydrocannabinol. When cannabis is heated in vacuum, the decarboxylation of tetrahydrocannabinolic acid (THCA) appears to follow first order kinetics. The log fraction of THCA present decreases steadily over time, and the rate of decrease varies according to temperature. At 10-degree increments from 100 to 140 C, half of the THCA is consumed in 30, 11, 6, 3, and 2 minutes; hence the rate constant follows Arrhenius' law, ranging between 10−8 and 10−5 in a linear log-log relationship with inverse temperature. However, modelling of decarboxylation of salicylic acid with a water molecule had suggested an activation barrier of 150 kJ/mol for a single molecule in solvent, much too high for the observed rate. Therefore, it was concluded that this reaction, conducted in the solid phase in plant material with a high fraction of carboxylic acids, follows a pseudo first order kinetics in which a nearby carboxylic acid participates without affecting the observed rate constant. Two transition states corresponding to indirect and direct keto-enol routes are possible, with energies of 93 and 104 kJ/mol. Both intermediates involve protonation of the alpha carbon, disrupting one of the double bonds of the aromatic ring and permitting the beta-keto group (which takes the form of an enol in THCA and THC) to participate in decarboxylation.
- Richard H. Wiley and Newton R. Smith. "m-Nitrostyrene". Org. Synth.; Coll. Vol., 4, p. 731
- March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.), New York: Wiley, ISBN 0-471-85472-7
- http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch19/ch19-3-4.html, Decarboxylation, Dr. Ian A. Hunt, Department of Chemistry, University of Calgary
- Jim Clark (2004). "The Decarboxylation of Carboxylic Acids and their Salts". Chemguide. Retrieved 2007-10-22.
- "Malonic Ester Synthesis". Organic Chemistry Portal. Retrieved 2007-10-26.
- "Does marijuana have to be heated to become psychoactive?".
- Perrotin-Brunel, Helene; Buijs, Wim; Spronsen, Jaap van; Roosmalen, Maaike J.E. van; Peters, Cor J.; Verpoorte, Rob; Witkamp, Geert-Jan (February 2011). "Decarboxylation of Δ9-tetrahydrocannabinol: Kinetics and molecular modeling". Journal of Molecular Structure. 987: 67. Bibcode:2011JMoSt.987...67P. doi:10.1016/j.molstruc.2010.11.061.
- "Archived copy". Archived from the original on 2008-03-26. Retrieved 2008-03-26.
- http://www.erowid.org/archive/rhodium/chemistry/tryptophan.html, Tryptamine from Tryptophan