A REVIEW OF SOME APPLICATIONS OF THE CANNIZZARO REACTION TO ALIPHATIC ALDEHYDES ROBERTC. ET,DERFIELD, MASSACHUSB~TS INSTITUTE OR TECHNOLOGY, CAMBRIDGE, MASSA~SBTTS
In the more popular of the current textbooks of organic chemistry, the group of compounds comprising the aldehydes are more or less sharply divided into two classes in the consideration of their deportment toward alkaline reagents. Aromatic aldehydes and those aliphatics with no alpha hydrogen, such as benzaldehyde, formaldehyde, and glyoxal, when subjected to the influence of alkali undergo what is known as the Cannizzaro Reaction-simultaneous oxidation and reduction of two molecules of the aldehyde with the formation of one molecule each of the corresponding alcohol and acid; the rest of the aliphatics condense with each other with the formation of aldols. Doubtless this differentiation has much to commend i t from a pedagogical point of view, but, a t the same time, the fact that typically aliphatic aldehydes can be made to display a behavior completely analogous to that of their aromatic prototypes appears in danger of being overlooked. To be sure, experimental conditions have to be modified somewhat in order to take into account the increased reactivity and tendency toward aldol formation consequent to the presence of an alpha hydrogen atom. But, when such allowances have been made, no intrinsic difference between the two classes is apparent, however striking may be the differences in degree. With the object of bringing out this capability of aliphatic aldehydes of undergoing $he Cannizzaro Reaction, the following summary of the literature bearing on the subject is presented. The first instance of the observation orf the action of an alkali upon a truly aliphatic aldehyde appears to have been that of Fittig' on valeraldehyde and heptaldehyde-eleven years before the discovery of the aldol condensation by Wurtz. He found that the former on standing six to seven weeks a t room temperature, or a few hours on the water-bath a t 100°, with calcium oxide gave iso-amyl alcohol and iso-valerianic acid as chief products; heptaldehyde upon similar treatment gave heptyl alcohol and heptylic acid. Between this time and 1898 several isolated investigations were undertaken, chiefly upon iso-butyric aldehyde. Pfeiffer,% Urech,3 W. H. Perkin, Jr.,' and Urbain6 studied the question, and their results, while not in complete agreement, did much toward clearing up the situation. In 1898, Franke and Kohn,Bworking with iso-butyric aldehyde carefully purified by
' Fittig.A n n . 117,68 (1861).
'
~feiffer,Ber., 5, 699 (i872j. Urech. I M . , 12, 191,1744 (1879): 13.483.590 (188% W. H. Perkin, Jr., Ibid., 15,2802 (1882);~.&em. ~ o c . ,43, 90 (1883); I%.,
210,1029 (1883). Urbain, Bull. (3) 13,1048 (1895). fianke and Kahn, Monatr., 19,354 (1898). 594
16,
V ~ L 7, . No. 3
595
APPLICATIONS OFCANNIZZAKO REACTION
depolymerization of the paraldehyde, reached the conclusion that under the influence of potassium hydroxide, its behavior may be represented:
CHa CH. )cH.cHoH.L.cH..oH
+C H > ~ o ~
I
CHa
CHa
CH1
Thus the situation rested for three years when Lieben and Zeissel' attempted further clarification, and put forward what has come to be known as the "Lieben and Zeissel Rule." The aldehydes were divided into three classes, viz.: I. Those with a CH2or CHs group adjacent todhe carbonyl group. These first undergo aldolization, and then lose water to give unsaturated aldehydes: 2CHaCH0 +CHaCHOHCHrCHO CH..CHOH.CHrCHO +CHVCH:C H C H O f Hz0
11. Those with a CH group adjacent to the carbonyl group, which undergo aldolization only: CHs 2 C HH~ ) c ~ ---t . ~ C ~ ~ H CHs
a
>
.
~I
I
~
~
~
.
~
.
~
CHI
111. Those conlaining no alpha hydrogen. These undergo a straight Caanizzaro Reaction of simultaneous oxidation and reduction: 2HCHO
--+-
CHIOH f HCOOH
This generalization appears to have been retained intact in the contemporary texts. Lieben and Zeissel, Momts., 22,289 (1901).
~
~
596
JOURNAL OF CHEMICAL EDUCATION
MARCH, 1930
That very year a direct exception to this rule was noted.* Iso-butyric aldehyde, on heating with aqueous barium hydroxide in a sealed tube at 150' during the course of fourteen hours, is quantitatively converted to isobutyl alcohol and barium iso-bntyrate. Valeraldehyde exhibited a corresponding behavior. Shortly thereafter, iso-butyl alcohol and iso-butyric acid were found among the products formed on heating iso-butyric aldehyde with milk of lime a t 150°.s The Lieben and Zeissel Rule found itself in further difficulties when the discovery was made that very mild alkali, in the form of aluminum ethylate, without exception, induced the condensation of aldehydes, either aliphatic or aromatic, with the formation of esters.1o As the mechanism of the Cannizzaro Reaction is ordinarily considered, this is the first step. Further work on this condensation has been plentiful in recent years.ll.12 Nord, by using mixtures of two different aldehydes, either two aliphatics or one aliphatic and one aromatic, obtained mixed esters under the influence of aluminum ethylate.13 Finally, this type of dismutation can be brought about by enzymes, first noted by Parnas." Since then the enzymatic transformations of aldehydes have been the subject of somewhat exhaustive study. Euler and his co-workers15~1E~17 conclude that the reaction is a function of the hydrogenion concentration of the medium, occurring to some extent in the region around pH 3 to 4, but more rapidly in the vicinity of pH 7. Further a co-enzyme seems to be necessary. The dismutation of aldehydes is regarded as a process by which two molecu\es of the aldehyde are simultaneously bound in such a way that one component is richer in energy than the other. When rupture of this new molecule takes place, it will do so in accordance with this distribution of energy. Thus it would seem that, contrary to the common impression, aliphatic aldehydes actually are capable of behavior similar to the aromatic ones, the reagent used to induce the Cannizzaro condensation having to be modified to a greater or less extent as befits the greater chemical reactivity of the former class. Otherwise there is no fundamental difference between the two.
.
Lederer, Monets., 22, 536 (1901). Henmann, Ibid., 25, 188 (1904). 10 Tischtschenko, Centrdblatt, 1906,II, 1309,1554,155G. 1' Child and Atkins, 3. Am. Chem. Soc., 4 5 3 0 (1923). Verley. Bull. (4) 35,487 (1924); (4) 41,788 (1927). la Nord, Bioch. 2 .. 106,275 (1920). I4 Pamas, Ibid.,28,290 (1910). 1' Josephson and v. Euler, Zeit. Physiol. Chirn., 135, 49 (1924). Myrbiick and Jacobi, IKd., 161,245 (1926). l7 v. Euler and Myrbick, IKd., 165,28 (1927).
