4.10: Reactions with cyclic transition state

Introduction to Organic and Biochemistry · LibreTexts

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    Learning Objectives
    • Learn examples of reactions that involve five- or six-member transition state, including cyclonic hemiacetal formation of monosaccharides, Diels-Alter reactions producing six-membered cyclic products, and decarboxylation of \(\beta\)-keto acids.

    Intramolecular reactions happen if the two reacting groups are on the same molecule and can come to a bonding distance through a five- or six-member cyclic transition state. Some examples of it are described in the next sections.

    Cyclic hemiacetal formation of monosaccharides

    Monosaccharides, like glucose, fructose, galactose, etc., have a \(\ce{C=O}\)-group on one \(\ce{C}\) and \(\ce{-OH}\)-group on every other \(\ce{C}\). \(\ce{-OH}\)-group can add to \(\ce{C=O}\)-group forming a hemiacetal. Monosaccharides exist primarily in a five- or six-membered hemiacetal form because one of their \(\ce{-OH}\)-group can form a five- or six-membered transition state for the reaction, as shown in Figure \(\PageIndex{1}\) for the case of D-glucose and D-fructose.

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    Figure \(\PageIndex{1}\): Illustration of five- or six-member cyclic hemiacetal formation of D-glucose and D-fructose through a cyclic transition state. (Copyright; Glucose: Calvero (talk · contribs), Public domain, via Wikimedia Commons, and Fructose: Vaccinationist, Public domain, via Wikimedia Commons)

    Diels–Alder reaction

    A conjugated diene, e.g., butadiene, and an alkene, e.g., ethene, make a cyclic six-member transition state. They react by the Diels-Alder reaction mechanism and produce a six-member cyclic product. This reaction can be intermolecular, e.g., between butadiene and then, or intramolecular, e.g., in the biosynthesis of antibiotic lovastatin, illustrated in Figure \(\PageIndex{2}\).

    clipboard_e267eaef8be0d04bafa3514e79cfe6c69.png
    clipboard_e21b160d2ba45e7177fedc470dd627c41.png
    Figure \(\PageIndex{2}\): Mechanism of Diels-Alter reaction illustrated with the example of reaction between butadiene and ethene (left) and biosynthesis of lovastatin (right). Three \(\pi\)-bonds break, and two \(\sigma\)-bonds and one \(\pi\)-bond form, shown in blue. (Copyright: Public domain)

    Decarboxylation

    Decarboxylation is the removal of carbon dioxide (\(\ce{CO2}\)) from a carboxylic acid (\(\ce{R-COOH}\)), as in this example: \(\ce{R-COOH ->[\Delta] R-H + CO2}\).

    This reaction requires high temperatures, such as in the thermal decomposition process. However, if there is a second carbonyl (\(\ce{C=O}\))) group \(\beta\}\) to the \(\ce{-COOH}\) group, it can easily acquire a six-member transition state and decarboxylate at moderate temperatures, as illustrated in Figure \(\PageIndex{3}\).

    clipboard_e9fe115f5154d9978fb4ea2fc0e646036.png
    Figure \(\PageIndex{3}\): Decarboxylation mechanism of \(\beta\)-keto carboxylic acids illustrated with the example decarboxylation of acetoacetic acid. (Copyright: Public domain).
    Ketone bodies and diabetes mellitus

    Acetoacetic acid and its reduced product \(\beta\)-hydroxybutyric acid, shown below, are produced in the liver as a result of the metabolism of fatty acids and some amino acids.

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    Acetoacetic acid and \(\beta\)-hydroxybutyric acid are called ketone bodies. Their concentration in the blood of healthy persons is about 0.01 mmol/L but in persons suffering from starvation or diabetes mellitus may be up to 500 times higher.

    Carboxylic acids exist as carboxylate anions under physiological conditions. Decarboxylation of the \(\beta\)-keto carboxylates happens spontaneously under physiological conditions. For example, acetoacetate decarboxylates and produces carbon dioxide and acetone, as illustrated in Figure \(\PageIndex{4}\).

    clipboard_e6ea4658a47c22f1323e7fd993110e962.png
    Figure \(\PageIndex{4}\): Illustration of decarboxylation mechanism with the example of acetoacetate converting into carbon dioxide and acetone. (Copyright; Public domain)

    Carbon dioxide leaves under moderate conditions in this case because the anion left behind is in resonance with the \(\beta\)-\(\ce{C=O}\) group. The body does not metabolize acetone but exhales through the lungs. Acetone is responsible for its characteristic sweet smell in the breath of people with swear diabetes.

    This page titled 4.10: Reactions with cyclic transition state was last modified on Thu, 21 Sep 2023 16:54:14 GMT and is shared under a Public Domain license and was authored, remixed, and/or curated by Muhammad Arif Malik.