For the free acids, conditions that deprotonate the carboxyl group (possibly protonating the electron-withdrawing group to form a zwitterionictautomer) accelerate decarboxylation.[7] A strong base is key to ketonization, in which a pair of carboxylic acids combine to the eponymous functional group:[8][3]
As described above, most decarboxylations start with a carboxylic acid or its alkali metal salt, but the Krapcho decarboxylation starts with methyl esters. In this case, the reaction begins with halide-mediated cleavage of the ester, forming the carboxylate.
In biochemistry
Decarboxylations are pervasive in biology. They are often classified according to the cofactors that catalyze the transformations.[11]Biotin-coupled processes effect the decarboxylation of malonyl-CoA to acetyl-CoA. Thiamine (T:) is the active component for decarboxylation of alpha-ketoacids, including pyruvate:
T: + RC(O)CO2H → T=C(OH)R + CO2
T=C(OH)R + R'COOH → T! : + RC(O)CH(OH)R'
Pyridoxal phosphate promotes decarboxylation of amino acids. Flavin-dependent decarboxylases are involved in transformations of cysteine.
Iron-based hydroxylases operate by reductive activation of O2 using the decarboxylation of alpha-ketoglutarate as an electron donor. The decarboxylation can be depicted as such:
Synthesis of saturated fatty acids via fatty acid synthase II in E. coli
Straight-chain fatty acid synthesis occurs by recurring reactions involving decarboxylation of malonyl-CoA.[12]
Case studies
Tetrahydrocannabinolic acid. The decarboxylation of this compound by heat is essential for the psychoactive effect of smoked cannabis, and depends on conversion of the enol to a keto group when the alpha carbon is protonated.
Upon heating, Δ9-tetrahydrocannabinolic acid decarboxylates to give the psychoactive compound Δ9-Tetrahydrocannabinol.[13] 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 precipitates 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.[14]
In beverages stored for long periods, very small amounts of benzene may form from benzoic acid by decarboxylation catalyzed by the presence of ascorbic acid.[15]
The addition of catalytic amounts of cyclohexenone has been reported to catalyze the decarboxylation of amino acids.[16] However, using such catalysts may also yield an amount of unwanted by-products.
^Hashimoto, Mitsunori; Eda, Yutaka; Osanai, Yasutomo; Iwai, Toshiaki; Aoki, Seiichi (1986). "A Novel Decarboxylation of α-Amino Acides. A Facile Method of Decarboxylation by the Use of 2-Cyclohexen-1-one as a Catalyst". Chemistry Letters. 15 (6): 893–896. doi:10.1246/cl.1986.893.