39%
ARTHURP. PHILLIPS [CONTRIBUTION FROM THE WELLCOME
Vol. TO
RESEARCH LABORATORIES]
The Condensation of Aromatic Aldehydes with 2-Ethylpyridine and with 4-Ethylpyridine BY ARTHURP. PHILLIPS RECEIVED FEBRUARY 16, 1954
A series of aromatic aldehydes has been condensed with 2-ethylpyridine and with 4-ethylpyridine in the presence of refluxing acetic anhydride as the condensing agent. The aldehydes were selected to represent a broad spectrum of carbonyl reactivity from @-nitrobenzaldehyde with a high carbonyl reactivity, through benzaldehyde, to p-dimethylaminobenzaldehyde with a very low order of inherent carbonyl reactivity. LVhile 2-ethylpyridine gave good yields of condensation products n i t h aldehydes of high carbonyl reactivity and with benzaldehyde, only traces of product or no reaction resulted with aldehydes of low reactivity such as p-methoxy- and p-dimethylaminobenzaldehyde. 4-Ethylpyridine gave very satisfactory yields with all of the aldehydes used, although the yields still paralleled the reactivity of the carbonyl groups of the aromatic :iltiehydes: p-NOp > nz-NO2 > H > p-CH30 > p-(CHa)*N.
I t has long been known that 2-methylpyridine? and 4-methylpyridine3 are reactive for condensation with aromatic aldehydes. Kaufmann and T:allette4 have shown that the quaternary salts of the 2-methylpyridines and quinolines react more readily and under milder conditions in condensation reactions than do the parent tertiary amines. -halogous condensations between 2-ethylpyridine or 4-ethylpyridine, or their methiodides, and aromatic aldehydes have not been reported. Earlier work from these laboratories reported the ready condensation of 2-methylpyridine methiodidej and 4-methylpyridine methiodide6 with a series of aromatic aldehydes. Under similar reaction conditions no condensation occurred between "ethylpyridine methiodidel and certain aromatic aldehydes. The methiodide was used in this greater reacearlier work7 because of the tivity of quaternary salts over their parent tertiary amines. $-Dimethylaminobenzaldehyde is, and would be expected to be, an aldehyde of very low carbonyl reactivity.* Xevertheless, in addition to benzaldehyde this was chosen as the principal carbonyl reactant in the attempted reaction with 2ethylpyridine methiodide7 because of the outstandingly superior yields obtained from it with 2methyl5 and 4-methylpyridine methiodide.6 Failure in these attempts to condense 2-ethylpyridine methiodide with aromatic aldehydes was attributed principally to steric hindrance to the reaction associated with the extra methyl group now located on the reactive methylene position. Steric factors, if responsible for the lack of condensation with 2-ethylpyridine methiodide, could interfere with either the initial attack of the reactive methylene component on the carbonyl carbon and/or with the resonance possibilities in the final products. Steric hindrance to the initial (1) This paper is P a r t I V of t h e series: Correlation of structure and reactivity of aromatic aldehydes. (2) (a) E. Jacobsen a n d C. L. Reimer, Ber., 16, 2602 (1883): ( h ) 11. Baurath, ibid., 20, 2719 (1887); 21, 818 (1888); (c) K. Feist. ibid., 34, 464 (1901); (d) K . Feist, Auch. Phaum., 240, 244 (1902); (e) A . I,adenburg, Ber., 36, 118 (1903); (f) 9.Ladenburg and E. Kroener, i h i d . , 36, 119 (1903), and many others. (3) (a) C. FriedlLnder, ibid., 38, 159 (1905); (b) K. Friedlander, ibid., S8, 2838 (1905); (c) R. Baumert, ibid., 39, 2971 (1906). :
