On the Mechanism of the Cannizzaro Reaction
Abstract Generated abstract
This paper reviews proposed mechanisms for the Cannizzaro reaction and evaluates them against reported reactions of aldehydes under alkaline, alcoholate, and related catalytic conditions. After discussing hydration, redox, addition-product, benzoin-intermediate, and ester-formation interpretations, it argues that the reaction is best understood through condensation of two aldehyde molecules to form an ester, followed by alkaline saponification to the alcohol and acid salt. The author proposes that aldehydes may condense in alternative directions, with catalyst and reaction conditions determining whether benzoin-type products, ester products, or related transformations predominate. This scheme is also applied to aliphatic aldehydes and glyoxal, and is presented as consistent with Tishchenko’s observations on the limits of ester condensation.
Full Text
L. N. Dyakonova-Shul’ts.
From the Laboratory of Organic Chemistry of the Siberian Technological Institute.
On the Mechanism of the Cannizzaro Reaction
Several assumptions have been put forward concerning the mechanism of the Cannizzaro reaction.
Wöhler and Liebig1 first indicated that, under the action of an alcoholic solution of caustic potash on benzoic aldehyde, potassium benzoate and an oil are formed; this oil was not investigated by them.
The same transformation was observed by Gerhardt and Cahours2 under the action of caustic potash on cuminic aldehyde; the oil formed together with potassium cuminate was likewise not investigated by them, but they tentatively gave the following explanation of the reaction:
\[ \mathrm{C_6H_{12}O + KOH = C_{10}H_{11}OK + H_2O} \]
\[ \mathrm{C_{10}H_{11}OK + H_2O = C_{10}H_{11}O_2K + H_2} \]
\[ \mathrm{C_{10}H_{12}O_2 + H_2 = C_{10}H_{14}O} \]
Cannizzaro3 was the first to establish the nature of the oil; it proved to be benzyl alcohol. This showed that one molecule of the aldehyde is reduced to an alcohol, while the other is oxidized to an acid.
V. Meyer4 found that, under the action of strong alcoholic solutions of caustic potash and caustic soda on benzoic aldehyde, benzyl alcohol and potassium benzoate are obtained. He explains the mechanism of the Cannizzaro reaction as follows:
\[ \begin{array}{rcl} \mathrm{C_6H_5{-}CH{=}O} & \quad \mathrm{H_2} \quad & \mathrm{C_6H_5{-}CH_2OH} \\ \mathrm{C_6H_5{-}CH{=}O} & \quad \mathrm{O} \quad & \mathrm{C_6H_5{-}COOH} \end{array} \quad \begin{array}{c} \\[-1.5em] + \ \longrightarrow \\ \\[-1.5em] \end{array} \]
that is, he considers that aldehydes in alkaline solutions add the elements of water, whereby one portion of the aldehyde is reduced and the other oxidized.
The participation of water in the Cannizzaro reaction is also considered necessary by A. E. Favorskii,^1) but he alone does not regard it as a reaction of simultaneous reduction and oxidation. A. E. Favorskii interprets the mechanism of the Cannizzaro reaction as follows:
\[ \begin{gathered} \begin{array}{c} \mathrm{C_6H_5CH{=}O}\\ \mathrm{C_6H_5CH{=}O} \end{array} + \begin{array}{c} \mathrm{H\,OH}\\ \mathrm{H\,OH} \end{array} \longrightarrow \begin{array}{c} \mathrm{C_6H_5CH}\begin{matrix}\mathrm{OH}\\[-2pt]\mathrm{OH}\end{matrix}\\[6pt] \mathrm{C_6H_5CH}\begin{matrix}\mathrm{OH}\\[-2pt]\mathrm{OH}\end{matrix} \end{array} \longrightarrow \begin{array}{c} \mathrm{C_6H_5{-}CHOH}\\ \phantom{\mathrm{C_6H_5{-}}}\backslash \mathrm{O}\\ \mathrm{C_6H_5{-}CHOH} \end{array} \longrightarrow \begin{array}{c} \mathrm{C_6H_5CH_2OH}\\ \mathrm{C_6H_5COOH} \end{array} \end{gathered} \]
In Nef’s opinion,^2) from benzoic aldehyde in the presence of alkali and alcohol there is first formed an addition product:
\[ \mathrm{C_6H_5{-}CH{=}O + C_2H_5OH \longrightarrow C_6H_5{-}CH(OH){-}OC_2H_5,} \]
which, with another particle of aldehyde, passes into an intermediate product:
\[ \mathrm{C_6H_5{-}CH(OH){-}OC_2H_5 + C_6H_5{-}CH{=}O \longrightarrow C_6H_5{-}COH(OC_2H_5){-}CHOH{-}C_6H_5,} \]
the latter, under the influence of weak alkali (KCN), loses alcohol and gives benzoin, while in the presence of a stronger alkali or sodium ethylate it is cleaved into benzoic acid and benzyl alcohol:
\[ \mathrm{HO{-}C(C_6H_5)(OC_2H_5){-}CHOH{-}C_6H_5 + H\,OH \longrightarrow C_6H_5COH{=}O + C_2H_5OH + C_6H_5CH_2OH} \]
Claisen^3) found that, under the influence of sodium methylate, benzoic aldehyde gives an intermediate product:
\[ \mathrm{ C_6H_5{-}C(OCH_3)(ONa){-}O{-}CH_2{-}C_6H_5, } \]
1) Zh. R. F. Kh. O. 27, 44.
2) J. U. Nef, Lieb. Ann. 287, 312.
3) L. Claisen, Ber. 20, 646.
which is decomposed by water into benzoic acid and benzyl alcohol; upon decomposition with glacial acetic acid and upon heating it is converted into benzyl benzoate and alcoholate:
\[ 2\,\mathrm{C_6H_5CHO}+\mathrm{CH_3ONa} \;\longrightarrow\; \mathrm{C_6H_5{-}C(ONa)(OCH_3){-}O{-}CH_2{-}C_6H_5} \]
\[ \mathrm{C_6H_5{-}C(ONa)(OCH_3){-}O{-}CH_2{-}C_6H_5} \;\longrightarrow\; \mathrm{C_6H_5{-}C(=O){-}O{-}CH_2{-}C_6H_5} +\mathrm{CH_3ONa} \]
A similar view is expressed by Ch. Kohn and W. Trenton;1 they obtained this same ester by the action of a concentrated aqueous solution of caustic soda on an excess of benzaldehyde. These authors suppose that, upon addition of a small amount of caustic soda to benzaldehyde, a compound is formed:
\[ \mathrm{C_6H_5{-}C \begin{matrix} <\,\mathrm{ONa}\\[-2pt] <\,\mathrm{OH} \end{matrix} \bigl(OCH_2{-}C_6H_5\bigr)} \]
similar to that of Klyuchnikov. In the presence of water it decomposes according to the equation:
\[ \mathrm{ \begin{matrix} \mathrm{OH}\\[-2pt] |\\[-2pt] C_6H_5{-}C{-}ONa\\[-2pt] |\\[-2pt] O{-}CH_2{-}C_6H_5 \end{matrix} \;+\; \begin{matrix} \mathrm{H}\\[-2pt] |\\[-2pt] \mathrm{O}\\[-2pt] |\\[-2pt] \mathrm{H} \end{matrix} \;\longrightarrow\; C_6H_5COONa+H_2O+C_6H_5CH_2OH } \]
in the absence of water the decomposition proceeds in two ways:
I.
\[ \mathrm{ \begin{matrix} &\mathrm{ONa}\\[-2pt] &|\\[-2pt] C_6H_5COH\\[-2pt] &|\\[-2pt] &\mathrm{OCH_2{-}C_6H_5} \end{matrix} \;\longrightarrow\; C_6H_5C \begin{matrix} \mathrm{O}\\[-2pt] \mathrm{ONa} \end{matrix} + C_6H_5CH_2OH } \]
II.
\[ \mathrm{ \begin{matrix} &\mathrm{OH}\\[-2pt] &|\\[-2pt] C_6H_5{-}CONa\\[-2pt] &|\\[-2pt] &\mathrm{OCH_2{-}C_6H_5} \end{matrix} \;\longrightarrow\; C_6H_5{-}C(=O){-}O{-}CH_2{-}C_6H_5 + NaOH } \]
Nef¹) offers yet another explanation. Benzaldehyde, in the presence of an aqueous alkali solution, adds water with formation of a hydrate:
\[ \mathrm{C_6H_5{-}CH{=}O + H'OH \longrightarrow C_6H_5{-}CH(OH)_2,} \]
which, losing water, is converted into \(\mathrm{C_6H_5{-}COH}\); the latter decomposes water with formation of the orthohydrate of benzoic acid and hydrogen:
\[ \mathrm{C_6H_5COH + H'OH \longrightarrow C_6H_5C(OH)_3 + H_2} \]
The orthohydrate decomposes into water and benzoic acid, while the hydrogen reduces the aldehyde to the alcohol:
\[ \mathrm{C_6H_5{-}C(OH)_3 \longrightarrow C_6H_5{-}C(=O)OH + H_2O} \]
\[ \mathrm{C_6H_5{-}CH{=}O + H_2 \longrightarrow C_6H_5{-}CH_2OH} \]
Forkran²) found that water-containing glyoxal, on heating, passes into glycolide and then into glycolic acid:
\[ \begin{gathered} \mathrm{CH{=}O}\\ \mathrm{|}\\ \mathrm{CH{=}O} \end{gathered} \longrightarrow \begin{gathered} \mathrm{CH_2}\\ \mathrm{>} \mathrm{O}\\ \mathrm{C}\\ \mathrm{O} \end{gathered} ;\quad \begin{gathered} \mathrm{CH_2}\\ \mathrm{>} \mathrm{O}\\ \mathrm{C}\\ \mathrm{||}\\ \mathrm{O} \end{gathered} +\mathrm{H\,OH} \longrightarrow \begin{gathered} \mathrm{CH_2OH}\\ \mathrm{|}\\ \mathrm{COOH} \end{gathered} \]
V. Meyer and A. E. Favorskii explain the transformation of glyoxal into glycolic acid by the above-described schemes.
V. E. Tishchenko³) found that, under the action of the alcoholates of magnesium, zinc, and aluminum on aliphatic and aromatic aldehydes, an ester condensation occurs, as in Claisen’s experiments with benzaldehyde. He asserts that the Cannizzaro reaction takes place in two
¹) J. U. Nef, Lieb. Ann. 298, 301.
²) Bull. Soc. Ch. Par. 41, 242.
³) Ж. Р. Ф. Х. О. 38, 382.
phase: first an ester is formed, and then it is decomposed by alkali into an alcohol and the salt of an acid.
\[ \begin{aligned} \text{I.}\qquad &\begin{matrix} R-\mathrm{CH}=O\\ R-\mathrm{CH}=O \end{matrix} \quad \longrightarrow \quad \begin{matrix} R-\mathrm{CH}_2\\ \ \ \ |\\ O-C-R\\ \ \ \ ||\\ \ \ \ O \end{matrix} \end{aligned} \]
\[ \begin{aligned} \text{II.}\qquad &\begin{matrix} R-\mathrm{CH}_2\\ \ \ \ |\\ O-C-R\\ \ \ \ ||\\ \ \ \ O \end{matrix} +KOH \quad \longrightarrow \quad R-\mathrm{CH}_2OH + \begin{matrix} \ \ \ O\\ R-C\!\!\!\!\diagup \ \\ \ \ \ OK \end{matrix} \end{aligned} \]
A. Lieben and A. Franke1 assumed that in all cases in which the Cannizzaro reaction is applicable, the aldehyde is first converted into an ester, which is then saponified into an alcohol and an acid.
Similar views are expressed by A. E. Chichibabin2 and S. N. Reformatskii3. Thus Chichibabin indicates that the Cannizzaro reaction is a special case of the reaction discovered by Tishchenko, i.e. benzaldehyde under the influence of caustic potash gives benzyl benzoate, which by the action of the same alkali is saponified, decomposing into an alcohol and the salt of an acid.
V. E. Tishchenko, L. Woelz, and I. Rabtsevich-Lubovsky4, studying the action of sodium alcoholates on
\[
\mathrm{C_6H_5-CH}
\quad
\mathrm{C_6H_5-C-OCH_3,}
\quad
\mathrm{C_6H_5-C-OC_2H_5,}
\]
\[
\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ O
\qquad\qquad
\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ O
\qquad\qquad
\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ O
\]
\[
\mathrm{C_6H_5-C-O-CH_2-C_6H_5}
\quad \text{and} \quad
\mathrm{C_6H_5-C-OC_5H_{11}}
\]
\[
\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ O
\qquad\qquad\qquad
\ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ O
\]
under the conditions described by Claisen, showed that in all cases \(\mathrm{C_6H_5COONa}\) is formed, and not addition products; it was further found that \(\mathrm{C_6H_5COONa}\) is not obtained at low temperature from the alcoholate and the ester of benzoic acid; moreover, they indicated that the water present in the alcohol decomposes the alcoholate, and the alkali thus formed saponifies the ester. Thus Claisen’s explanation for the Cannizzaro reaction proved unacceptable. The authors indicate that
\[
\mathrm{C_6H_5-CH}
\]
\[
\ \ \ \ \ \ \ \ \ \ \ \ O
\]
under the influence of alcoholates condenses in an unknown manner into \(\mathrm{C_6H_5-COO-CH_2-C_6H_5}\). When water acts on this mixture, alkali is obtained (from the alcoholate),
which
\[ \mathrm{C_6H_5C(=O)-O-CH_2C_6H_5} \]
is readily saponified; if water is replaced by acetic acid, then the alcoholate passes into the acetate and
\[ \mathrm{C_6H_5-C(=O)-O-CH_2-C_6H_5} \]
is not saponified.
Under the influence of certain reagents, aldehydes, as is known, give a condensation of another type, with complication of the carbon skeleton of the molecule. For example, benzaldehyde, under the action of a solution of potassium cyanide, passes into benzoin. This reaction proceeds, evidently, according to the scheme:
\[ \mathrm{C_6H_5-CH(=O) + H-C(=O)-C_6H_5 \;\longrightarrow\; C_6H_5-CH(OH)-C(=O)-C_6H_5} \]
B. V. Tronov\(^1\) expressed the idea that benzoin may be an intermediate product in the Cannizzaro reaction, since the further action of alkali might quite well lead to benzyl alcohol and the salt of benzoic acid:
\[ \mathrm{C_6H_5-CH(=O) + C_6H_5-CH(OH)(=O) \;\longrightarrow\; C_6H_5-CH(OH)-C(=O)-C_6H_5 + KOH} \]
\[ \mathrm{\longrightarrow\; C_6H_5-CH(OH)-C(OK)-C_6H_5 \;\longrightarrow\; C_6H_5-CH_2OH + C_6H_5-C(=O)OK} \]
There is an indication in the literature\(^2\) that benzoin actually decomposes in the presence of alkalis into the acid salt and alcohol. However, the unquestionable formation of benzyl ester of benzoic acid in experiments with alcoholates\(^3\) cannot be explained in this way. One can arrive at a very simple scheme if one assumes that two molecules of benzaldehyde combine with one another not as occurs in the formation of benzoin, but in the opposite direction; the hydrogen of the second molecule goes to the carbon of the first, and the residue attaches to the oxygen; then benzyl ester of benzoic acid is obtained:
\[ \mathrm{ C_6H_5-CH(=O) + H-C(=O)-C_6H_5 \;\longrightarrow\; C_6H_5-CH_2-O-C(=O)-C_6H_5 } \]
\(^1\) Izvestiya Tomskogo Tekhnologicheskogo Instituta, vol. 45 (1924).
\(^2\) Arthur Lachman, C. 1923 III 1271.
\(^3\) Carbide u. Carbon Chemicals Corporation, assigned by Charles O. Young C. 1927 II 1621 A. P. 1630593 (1925).
It must be supposed that aldehydes in general can condense in both directions, and that the nature of the catalyst, as well as other conditions, determines which of these reactions will predominate in each given case.
Thus A. Lachman1 indicates that, on heating benzaldehyde to \(300^\circ\), the Cannizzaro reaction takes place; benzyl or benzoin is not formed. Under the action of KCN in the presence of a small quantity of water, however, benzoin condensation occurs.
In exactly the same way, aldehydes of the fatty series, besides the usual aldol condensation, can quite well react with the formation of an ester according to the scheme:
\[ \begin{array}{c} \mathrm{CH_3{-}CH} \quad + \quad \mathrm{H{-}C{-}CH_3} \\[-0.2em] \ \ \ \Vert \qquad\qquad\quad \Vert \\[-0.2em] \ \ \ \mathrm{O} \qquad\qquad\quad \mathrm{O} \end{array} \;\longrightarrow\; \mathrm{CH_3{-}CH_2{-}O{-}C(=O){-}CH_3} \]
The interpretation of the Cannizzaro reaction proposed here explains well the results of the experiments of V. E. Tishchenko,2 who showed that ketones, paraldehyde, and acetal are incapable of ester condensation.
In glyoxal, ester condensation proceeds within one and the same molecule:
\[ \begin{array}{c} \mathrm{H{-}C{=}O} \\ \mathrm{H{-}C{=}O} \end{array} \;\longrightarrow\; \begin{array}{c} \mathrm{CH_2} \\[-0.2em] \diagdown\!\!\!\!\!\!\diagup\ \mathrm{O} \\[-0.2em] \mathrm{C} \\[-0.2em] \Vert \\[-0.2em] \mathrm{O} \end{array} \]