User:Anonymousecat/Krapcho decarboxylation
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| Krapcho decarboxylation | |
|---|---|
| Named after | A. Paul Krapcho |
| Reaction type | Substitution reaction |
| Identifiers | |
| RSC ontology ID | RXNO:0000507 |
Decarboxylation is commonly used for synthesis in organic chemistry and biochemistry.[1] Krapcho decarboxylation, one of its named reactions, is used to manipulate certain compounds.[2] It involves an ester-containing compound with an electron-withdrawing group (EWG) beta to the carbonyl group (See: Locant), a salt, water, and a dipolar aprotic solvent. The mechanism of this reaction is not yet fully understood. However, the suggested mechanisms are different depending on the substituents on the ester-containing compound.[3]
Reaction Scheme[edit]
Components of the Reaction[edit]
The four main components of the reaction are:
Salt
There are a variety of salts that were previously studied for Krapcho decarboxylation.[4] It is suggested that the salts were not necessary for reaction, but greatly accelerates the reaction when compared to the reaction with water alone. Some examples of salts used in the reaction are: NaCl, LiCl, KCN, and NaCN.
Solvent
The solvent used in Krapcho decarboxylation is dipolar aprotic. A commonly used solvent is dimethyl sulfoxide (DMSO), a polar aprotic solvent with a low dielectric constant. Such solvents destabilize the anion, making it a stronger nucleophile and hence suitable for attacking.[5]
Temperature
Like many decarboxylation reactions, the temperature for the Krapcho decarboxylation reaction needs to be high.[6][7] For the Krapcho reaction, the temperature needs to be kept at about 150 ºC for maximal results.[3]
Ester-containing compound
The ester must contain an EWG in the beta position for the Krapcho decarboxylation to take place. The reaction works best with a methyl group at R3,[3] which is a methyl ester, since methyl groups are more susceptible to SN2 reactions than larger alkane chains. However, the mechanism changes depending on the substituents R1 and R2.
Mechanisms[edit]
The mechanisms are still not fully uncovered. However, the following are suggested mechanisms for two different substituents:
α,α-Disubstituted Ester
For an α,α-disubstituted ester, it is suggested that the anion in the salt attacks the R3 in an SN2 fashion, kicking off R3 and leaving a negative charge on the oxygen. Then, decarboxylation occurs to produce a carbanion intermediate. The intermediate picks up a hydrogen from water to form the products.[3]
The byproducts of the reaction (X-R3 and CO2) are often lost as gases, which helps drive the reaction; entropy increases and Le Chatelier's principle takes place.
α-Monosubstituted Ester
For an α-monosubstituted ester, it is speculated that the anion in the salt attacks the carbonyl group to form a negative charge on the oxygen, which then cleaves off the cyanoester. With the addition of water, the cyanoester is then hydrolyzed to form CO2 and alcohol, and the carbanion intermediate is protonated.[8]
The byproduct of this reaction (CO2) is also lost as gas, which helps drive the reaction; entropy increases and Le Chatelier's principle takes place.
Advantages[edit]
The Krapcho decarboxylation is a comparatively simpler method to manipulate malonic esters because it cleaves only one ester group, without affecting the other ester group.[2] The conventional method involves saponification to form carboxylic acids, followed by decarboxylation to cleave the carboxylic acids, and an esterification step to regenerate the esters. [9] Additionally, Krapcho decarboxylation avoids harsh alkaline or acidic conditions.[10]
References[edit]
- ^ "m-nitrostyrene". Organic Syntheses. 33: 62. 1953. doi:10.15227/orgsyn.033.0062.
- ^ a b Krapcho, A. Paul; Glynn, Gary A.; Grenon, Brian J. (1967-01-01). "The decarbethoxylation of geminal dicarbethoxy compounds". Tetrahedron Letters. 8 (3): 215–217. doi:10.1016/S0040-4039(00)90519-7. ISSN 0040-4039. PMID 6037875.
- ^ a b c d Poon, Po. S.; Banerjee, Ajoy K.; Laya, Manuel S. (2011). "Advances in the Krapcho Decarboxylation". Journal of Chemical Research. 35 (2): 67–73. doi:10.3184/174751911X12964930076403. ISSN 1747-5198.
- ^ Krapcho, A. Paul; Weimaster, J. F.; Eldridge, J. M.; Jahngen, E. G. E.; Lovey, A. J.; Stephens, W. P. (1978-01-01). "Synthetic applications and mechanism studies of the decarbalkoxylations of geminal diesters and related systems effected in dimethyl sulfoxide by water and/or by water with added salts". The Journal of Organic Chemistry. 43 (1): 138–147. doi:10.1021/jo00395a032. ISSN 0022-3263.
- ^ Hansen, Thomas; Roozee, Jasper C.; Bickelhaupt, F. Matthias; Hamlin, Trevor A. (2022-02-04). "How Solvation Influences the S N 2 versus E2 Competition". The Journal of Organic Chemistry. 87 (3): 1805–1813. doi:10.1021/acs.joc.1c02354. ISSN 0022-3263. PMC 8822482. PMID 34932346.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Olejar, Kenneth J.; Kinney, Chad A. (2021). "Evaluation of thermo-chemical conversion temperatures of cannabinoid acids in hemp (Cannabis sativa L.) biomass by pressurized liquid extraction". Journal of Cannabis Research. 3 (1). doi:10.1186/s42238-021-00098-6. ISSN 2522-5782. PMC 8408919. PMID 34465400.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Dunn, Gerald E.; Thimm, Harald F. (1977-04-15). "Kinetics and mechanism of decarboxylation of some pyridinecarboxylic acids in aqueous solution. II". Canadian Journal of Chemistry. 55 (8): 1342–1347. doi:10.1139/v77-185. ISSN 0008-4042.
- ^ Krapcho, A. Paul; Jahngen, E. G. E.; Lovey, A. J.; Short, Franklin W. (1974-01-01). "Decarbalkoxylations of geminal diesters and β-keto esters in wet dimethyl sulfoxide. Effect of added sodium chloride on the decarbalkoxylation rates of mono- and di-substituted Malonate esters". Tetrahedron Letters. 15 (13): 1091–1094. doi:10.1016/S0040-4039(01)82414-X. ISSN 0040-4039.
- ^ Flynn, Daniel L.; Becker, Daniel P.; Nosal, Roger; Zabrowski, Daniel L. (1992-11-24). "Use of atom-transfer radical cyclizations as an efficient entry into a new "serotonergic" azanoradamantane". Tetrahedron Letters. 33 (48): 7283–7286. doi:10.1016/S0040-4039(00)60166-1. ISSN 0040-4039.
- ^ Krapcho, A. Paul (2007-04-12). "Recent synthetic applications of the dealkoxycarbonylation reaction. Part 1. Dealkoxycarbonylations of malonate esters". Arkivoc. 2007 (2): 1–53. doi:10.3998/ark.5550190.0008.201.