Vol. 73
J. B. CULUEKTSON
4818
and introduce (lo), we get
+ lnp
i t = A/[q]*"
This equation should give a straight line by plotting 1/ [?I*" against t. The experimental plotted data for the relation between t and 1/ in Fig. 1, show a linear relationship within the experimental error. The values of A were calculated from (11) by use of the experimental values of K and a. A / h was calculated from the slope of the straight line inaFig. 1. The values of X from these relations, as is shown in Table IV, almost agree with the values of X in the 4th column in Table 111.
5 ti0
r
w
e
.e
$*
( 12)
40
3
20
TABLE IV 'krill>
,
'C.
3 J
8
4 Fig. 1.-Plot
of l / [ q ] "
12
16
1/[?11". DS. t: -4-4-1, 30"; -X-X-X, 40"; -0-0-0, 50".
progresses, but they are nearly constant. Momover if we put in (7)
40 50
A
A/h
0 0115 ,00957 .00827
25.70 8.50 2.29
x x IO' 4.47 11 28
36.18
Acknowledgment.-The authors wish t o express their appreciation to Professor I. Sakurada for many illuminating discussions which were extremely helpful during the course of this investigation. SAGOYA, JAPAN
RECEIVED NOVEMBER G , 193J
[CUNTRIBUTION FROM THE DEPARTMENT OF CHEhlISTRY UF CORNELL COLLEGE]
Factors Affecting the Rate of Hydrolysis of Ketimines BY J. €3. CULBERTSON Earlier work on the preparation of ketimines (references 1, 2 and 4) has indicated wide variation in the ease of their hydrolysis to the corresponding ketones. Certain structural relations have appeared to be connected with this variation in rate of hydrolysis. It has been the purpose of this study to investigate some of these structural influences. To this end variously substituted diphenyl ketimine hydrochlorides have been prepared-their rates of hydrolysis, ultraviolet absorption spectra and ionization of the free ketimines as bases determined. Two types of substituent effects have appeared t o be established; (1) a tautomerism and/or resonance, and ( 2 ) steric hindrance. Two other intramolecular factors suggested from earlier work on ketimines, and analogous compounds, have been considered. They are: (1) the relative negativity of the radicals attached to the carbimino group, and (2) strength of the free ketimines as bases. From the data of this report there is only meager evidence for the operation of any such factors.
This report represents an investigation of the rates of hydrolysis of variously substituted diphenyl ketimines-as hydrochloride salts in dilute aqueous solution-to their corresponding ketones. +C1The general reaction is: [R-C(=NH~)-RI] HOH+R-CO-Rl+ NHd+Cl-. A number of reports has indicated wide variation in the rate of this hydrolysis with structural differences. The early work of Moureu and Mignonac' pointed out that diary1 ketimines were more stable toward hydrolysis than the alkyl aryl ketimines. They were unable to prepare dialkyl ketimines. Later work2 revealed striking effects of other structural difference^.^ Especially the
+
(1) C. Moureu and G Mlgnonar C o i n p i r e n d , 156, 1801 ( 1 9 I 3 ) , 169, 237 (1919). 170,936 (1920), .4nn Chrm , [YI 14, 322 (1920) (2) P Rruylaets, Bull V I arad roy B r l g , L5l 8, 7 (1922) Bull SOL chrm f M g , 39, 307 (1923), I. Hary, ; b i d , 31, 397 (1922), De Boosere, rbrd , 84, 26 (19231, R Breckpot, ~ b r d, 81, 386 (1923) and M Jaspers rbrd , 34, 182 (1925) (3) The extrdordlnarlly stable ethyl cyclopropyl ketiminc hydro chloride reported by DeBoosere wds shown by Cloke lo be the isoni~ric 1 ethylpyrroline salt (J €3 Cloke, Tms J O U R N A L , 61, 1174 (1929))
work of Hoesch4 on the preparation of polyhydroxy diphenyl ketones by way of intermediate ketimines has suggested the latter as much more stable toward hydrolysis than the unsubstituted diphenyl ketimine. To gain some idea of the structural relations involved, measurements have been made on the rates of hydrolysis and ionization constants as bases of a selected group of substituted diphenyl ketimines. Table I lists these data. Large variations in rates of hydrolysis are evident. Two factors have appeared t o play significant roles in affecting this sensitiveness of ketimines tow:ird hydrolysis : (1) a ketimine-enamine tautomerism and/or resonance, ( 2 ) steric hindrance (ortho-effect). (1) The imine-enamine tautomerism has been suggested by the early work of Collie5 and of Best (4) K Hoesch, Be? ,48, 1122 (1915); K Hoesch aud T V Zarzecki r b t d , 60, 462 (1917) ( 6 ) 1 Y Culhi J Clirru . ~ O L 71, 2(VJ J l l (18'J71
FACTORS AFFECTINGTHE RATEOF HYDROLYSIS OF KETIMINES
Oct., 1931
TABLE I
Ketiniine Diphenyl 2-Methyldiphenyl 3-Methyldiphenyl 4-Methyldiphenyl 2-Chlorodiphenyl 3-Chlorodiphenyl 4-Chlorodiphenyl 2-Hydroxydiphenyl 3-Hydroxydiphenyl 4-Hydroxydiphenyl 2-Methoxydiphenyl 3-Methoxydiphenyl 4-Methoxydiphenyl 2,4-Dimethyldiphenyl 2,5-Dimethyldiphenyl 3,5-Dimethyldiphenyl 2,6-Dimethyldiphenyl
Hydrolysis of hydrochloride, k" x 101 00 25O 5.5 77d 0.28' 4.2 5.4a 76d 33.8 2.6" 29 2.0 378d 27 129d 9.2b 12 125d 8.9 7 1.1 14.9 63d 4.5 1,4c 20d 3.5 3.7 50d 3.6 0.08 (at 100') 0.48
2,4-DihydroxydiphenyI 2-Methoxy-4-hydroxydiphenyl 2.4-Dimethoxydiphenyl 2,4,6-Trihydroxydiphenyl 2.4-Dihydroxy-6-met hyldivhenvl -
Basic Half-life strength, period, kb min. a t XI* X 100 9.0 150 62 165 9.1 20.5 23.9 3.9 1.8 4.9 5.4 57.8 1 .o 120 5.5 99 28 47 196 11 38 35 198 62 187 62 13.9 150 8670 19.5 (at 100') 1444 1.0
0.77 1.45 0.082
900 478 8450
9.8 2000 1.6
0.20
3466
56
Measured by Cloke and co-workers, Rensselaer Polytechnic Institute, Troy, N.Y.; refer t o Doctor's Dissertation, J. B. Cloke, Department of Chemistry, University of Chicago, 1931. * Measured by Ingle, Master's Thesis, Measured by B. White, University of Chicago, 1926. Master's Thesis, University of Chicago, 1927. d Calculated from value measured at O", assuming 14-fold increase for the 25-degree rise in temperature. a
and Thorpe.6 Moureu and Mignonac? gave support to such tautomerism in their observation t h a t such ketimines as ethyl phenyl ketimine could be converted into ketisoketimines and ammonia. Such a change would suggest a labile hydrogen on the carbon next to the carbimino group, thus (a) CGHS-C(=SH)-CH~CH, + (imine form)
t-
CBH~-C(-NH~)=CH-CH~ (amine form)
4819
them to display ketimine-enamine tautomerism and concluded that they existed principally as enamine^.^ In view of these considerations, Stieglitz suggested that the marked stability toward hydrolysis of the polyhydric diphenyl ketimine salts of Hoesch4 might be due to a benzoid-imine and quinoidamine tautomerism, as here illustrated for 2,4dihydroxydiphenyl ketimine salt ion 0-H
+
fiH3 9-quinoid-amine (A) 0-H
0
o-quinoid-amine (B)
benzoid-imine
Shift of phenolic "H" either from the para- or the ortho-position, to produce the quinoid-amine forms (A) or (B), may be considered possible, though the former is no doubt more probable. The quinoid-amine forms should not be subject to hydrolysis. Hence extensive existence in these forms might account for the slow speed of hydrolysis of the phenolic ketimines prepared by Hoesch. Such a tautomerism has been indicated by a comparative studylo of various properties of 2,4-dihydroxydiphenyl ketimine with those of its ortho-monomethyl and dimethyl ethers and with the unsubstituted diphenyl ketimine. Comparative rates of hydrolysis, colors of the free bases and salts, solubilities in different solvents, and other properties were uniformly found to suggest this tautomerism. Resonance between imine and aniine forms may be a concurrent stabilizing factor
( b ) C6H5--$-CHp--CHs
0-H
I!
A"
H H \/
H--h==&!-c& i -
heating
-+
++
I : NH2
s
0-H /..
CsHs--d=CH-cHa CGH~-C--CH~-CHB
/I I
..
H-Oe-C-CoH: II
Iz' CE.H~-C=CH-CH~ (a ketisoketimine)
4- NHa
The fact that ethyl phenyl ketimine may be converted quantitatively, on the one hand by heating into the ketisoketimine and ammonia, and on the other by hydrolysis to the ketone, furnishes quite definite evidence for this tautomeric relation. Through the study of certain physical data on the nitrogen analogs of ethyl acetoacetate and related compounds, Auwers and SusemihP considered (6) S. R. Best and J. F. Thorpe, J . Chcm. Soc., 91, 1506-1537 (l909), and other articles of a long series: J. F. Thorpe, Proc. Chem. Soc., 96, 309 (1910). (7) C. Moureu and G. Mignonac, Compl. r e n d . , 168, 1395-1400 (1914); 169, 149-152 (1914). (8) K. v. Auwers and W. Susemihl, Ller., 63, 1073 (1930).
++
/
H-O *. - D -=C-C~H~ I
:NHP (9) Closely related to the ketimines of this report is the dye, auramine. The dual behavior of this compound has suggested a tautomeric equilibrium for it
( CH~)~+NH-C~H,-C(=NH)-CCBH,N( CHa)z _c ( CH~)~+N=CBHI=C(-NH~)-CBH(N( CHa)r The first of these is a benzoid-imine (ketimine) and the second a quinoidamine structure. The fact that auramine undergoes a measurable (W.C. Holmes and J. F. Darling, THISJOURNAL, 46, 2343 (1924)), though slow,hydrolysis to Michler ketone indicates the benzoid-imine type of structure. (10) J. B. Culbertson, Doctor's Dissertation, University of Chicago, 1927.
4S20
J. H . CULBERTSON
VOl. 73
methyl- compound could not display tautomerism or resonance, this bit of evidence would suggest that the latter two compounds also do not, or only feebly, enter into this relation. (2) The second factor which has appeared affecting the stability of aromatic ketimines toward hydrolysis is that of steric hindrance. An examina0-€I 0-H tion of the ketimines listed in Table I reveals, apart from any tautomerism or resonance, some special effect of groups in ortho position to the +Ai1 :AH2 carbimino group. Of the three monohydroxyAn extension of this investigation suggested a diphenyl ketimines the hydrolysis rates of the oconsideration of the three monohydroxydiphenyl and p-substituted forms are not far different. ketimines. For this purpose these compounds, to- T h a t of the m-compound is very much faster. gether with their methyl ethers, have been prepared It may be expected, according to the tautomeric and studied. And as supplementary material, factor, that the p-compound should have a defitwo other polyhydric phenolic ketimines reported nitely slower rate than the o-compound. The by Hoesch, 2,4,6-trihydroxydiphenyland O-methyl- comparably slow rate for the o-form might be 2,4-dihydroxydiphenyl ketimines, have been in- due largely to steric hindrance. The three monocluded in the study. An inspection of hydrolysis methoxy diphenyl ketimines display a similar constants (Table I) for these phenolic ketimines relationship. As noted before resonance may reveals a very marked effect of hydroxy-groups account for the moderately slow rates for the p in para- and ortho-positions. It is of critical and o-methoxy-substituted compounds. However, importance to note that the 3-hydroxydiphenyl the retarding influence of the substituent in the ketimine is even more rapidly hydrolyzed than the o-position predominates to give this compound the unsubstituted diphenyl ketimine. Where there slower rate of hydrolysis. The hydrolytic rate of is no possibility of quinoid-amine structure, we the m-compound is again very much faster, where find the possible effect of increasing the rate of neither retarding influence of resonance nor steric hydrolysis due t o the base-weakening action of the hindrance can operate. The three monomethyldiphenyl ketimines furnish a still more striking phenolic group in the ketimine structure.11 Resonance would appear to be the prime factor illustration of o-substitution effect. Here no in the comparatively slow rates of hydrolysis dis- tautomerism or resonance can be involved. We played by the 2- and 4-methoxydiphenyl ketimines see that the rate of hydrolysis of the o-form is very much less than that of the other two forms, which are not far W e r e n t . A similar relation exists among the chloro-diphenyl ketimines. +s i i A comparison of the poly-substituted phenolic H J C 0'-- 0 - c Cdf5 ketimine hydrolysis rates furnishes additional + \-==l evidence of steric hindrance. The 2,4-dihydroxy:SI{" diphenyl ketimine has a slow rate of hydrolysis, due I'urtlier evideiicc on the existence of this keti- perhaps (as already pointed out) rather largely iiiine-enamine tautomerism, or resonance, has been to tautomerism. Both p- and o-quinoid tautomobtained in ultraviolet absorption spectra data. erism were mentioned as possible. The 2,4,6For this purpose a number of the ketimine salts trihydroxydiphenyl ketimine has an even slower listed in Table I were chosen for examination. rate than might be predicted on the basis of one The plotted absorption data are shown in Figs. more possible o-#-quinoid tautomerism. This 1, 2 and 3. These reveal a definite distinction extra slower rate may be due to the combined between those ketimines which might display retarding effects of two o-substituents, ie., to steric tautomerism or resonance and those which would hindrance. The 2,4-dihydroxy-6-methyldiphenyl not. Of the first group, 4-hydroxy-, 2,4-dihy- ketimine displays a distinctly slower rate of hydroxy- and 2,4 - dimethoxydiphenyl ketimine drolysis than the 2,4-dihydroxy compound. This hydrochlorides show pronounced absorption in increase in resistance to hydrolysis would appear to the general region of 260 to 380 mp. There be due to the retarding influence of a methyl group are two peaks of absorption within this region. in o-position. As a further check upon this pronounced retardThe 2-hydroxy- and 2-methoxydiphenyl ketimine salts show one peak of absorption around 275 111,~. ing effect of substituents in o-positions to the carIn the second group comprising those compounds bimino group of these ketimines, study was made which could not display tautomerism, namely, of four dimethyldiphenyl ketimines. With this diphenyl and the 3-hydroxy-, 3-methoxy-, 4- series there should be no tautomerism or resonance, methyl-, 2-chloro- and 4-chloro-diphenyl ketimine the basic strengths12 of the free ketimines are not hydrochlorides, one band of absorption with peak far different, and the relative negativities12 of the at about 250 nip appears. The 2-methyl- cotn- variously substituted dimethylphenyl radicals pound gives a band with peak at about 275 inp, should not vary much. Any pronounced differences just as shown by %hydroxy- and 2-inethoxv- in rates of hydrolysis would then appear attributtliphenyl ketimines. Since structurally the 2- able to steric hindrance. Reference to Table I However it may be expected that this shift of electron density from oxygen toward nitrogen should lead to the dropping of a proton by oxygen and the gain of one by the nitrogen. The net result would be tautomerism. A similar outcome could be realized from resonance of a phenolate ion
I
i
11 1 I liter riierclici t o Ihi= facto1
(12' T + ter r
