E.F. PR.4TT
4310
AND
J. LASKY
Vol. SS
[CONTRIBUTION FROM THE DEPARTMENT O F CHEMISTRY, UNIVERSITY
OF
MARYLAND]
Reaction Rates by Distillation. VII. The Relative Basicities of Selected Amides’ BY ERNESTF. PRATT AND JACK LA SKY^ RECEIVED NOVEMBER 4, 1955 The effects of 56 selected carboxy- and sulfonamides on the rate of selE-etherification of benzhydrol in the presence of p-toluenesulfonic acid in benzene solution have been determined. Changes in rate of nearly one hundred-fold resulted as the structure of the amide was varied at a concentration of 0.0156 molar. Good correlation was obtained between the decrease in rate of etherification and the decrease in the electron attracting ability of R as R was varied among NO2, C1, H, CH8 and CHIO in the following types of amides : p-RCeH4CONH2, p-RC6H4COSHCH3,p-RCeH4CON(CH&, p-RCsH4CO”C6Hj, CeH6CONHC6H4R-p, p-RCJ€4CONHC&J2-p, ~ - R C E , H ~ S O ~ N H Cand B H caH&O~”c&R-p. ~ The large decreases in etherification rate observed with most of the amides are ascribed t o their ability t o coordinate with and thereby deactivate the acid catalyst. All of the benzenesulfonamides and most of the chloro- and nitrobenzanilides, however, markedly increased the etherscation rate. Since these amides were found t o be too weakly acidic t o catalyze the etherification in the absence of the p-toluenesulfonic acid alternative explanations for their accelerating effects are briefly considered.
Relative basicities for a number of ketones, esters and ethers were previously determined by measuring the ability of these oxygen bases to coordinate with and thereby deactivate the p-toluenesulfonic acid used to catalyze the self-etherification of benz-
al -1.ii
-18
-
-3.0
h y d r ~ l . ~In, ~the present investigation the effects of 56 selected carboxy- and sulfonamides on the rate of the etherification were similarly investigated. One liter of a benzene solution containing 0.250 mole of benzhydrol, 0.001 mole of p-toluenesulfonic acid and 0.0156 mole of the amide was heated under reflux. The reaction, which is first order in the benzhydrol, was followed by observing the rate a t which the by-product water collected in a DeanStark trap. It is apparent from the data in Table I that a nearly one hundred-fold variation in rate constant occurred as the structure of the amide was varied. This contrasts sharply with the results of the earlier study3 in which the rate constant varied only about fourfold although the concentration of the oxygen bases in that study was eight times the concentration of the amides in this one. -1high degree of correlation between an increase in rate of etherification and an increase in the electron attracting ability of either substituent5 on the -CONH- or 4 0 2 ” group is apparent throughout Table I. In Fig. 1 it is shown that most of the results for the first eight groups of amides tabulated can be quantitatively correlated with the acidities of the corresponding benzoic acids as expressed by Hammett’s u constants.6,7 Such correlations would be the expected result of deactivation of the p-toluenesulfonic acid via association with the amides. For the present purposes the complex may be indicated as I since there is disagreement concerning whether the p-toluencsulfonic acid (HX) would be coordinated pre-
-3.2
H
H
I -0 2
0
+ O 2 0.4
U0
0.8
U
Fig 1.-Plot of the logarithm of the rate constant5 for etherification in the presence of: RC6H4SO2NHC&, 8; C$H$302NHCeH4R, 0;RCeHaCOSHC6Hj, 0 ; CeHjCOSHCeHaR, 8 ; RCeH4COTiHCsHaR,O; R C ~ H I C O N H C H ~0, ; RC6H4COr\’(CH3)2, 0 ; RCsH4COSH2,(3; (from Table 1) z w s u s Hammett’s sigma constants. *, the point, e , is for C 6 H s S O ~ ~ H C and & the point, 0 , is for CeH5CONHCeH5. (1) F o r t h e preceding article in this series see E. F. P r a t t and P. W. Erickson, THISJOURNAL, 7 8 , 76 (1936). ( 2 ) F r o m t h e P h D. thesis of Jack Lasky, J u n e , 1955
(3) E. F. P r a t t and Ken h l a t s u d a , THISJ O U R N A L , 7 6 , 3739 ( 1 0 5 3 ) . (4) L. A . \Tiles a n d E. C. Baughan, J. Chem. Soc., 933 (19531, give \-aluahle d a t a on t h e basicity of ketones a n d diketones. Their paper was unavailable in this country when t h e manuscript of reference 3 was submitted. A recent s u m m a r y of some of t h e extensive pioneering work of R. P. Bell a n d co-workers in this field may be found in “Advances in Catalysis,” Vol. IV, Ed. b y W. G. Frankenburg, \’. I. Komarewsky a n d E. K. Rideal, Academic Press, Inc., New York. pi. Y., 1952, pp. 201-207. ( 5 ) Revised values for t h e relative electron attracting abilities of a variety of groups are given b y H H. JaffC, Chem. Rcws., 53, 191 (1953). (13) I-. P H a m m e t t , “Physical Organic Chemistry,” XlcCraw-Hill Book Co., S e w York, N. Y . , 1940, p. 188. (7) I t u-ill be noted t h a t t h e points for two of t h e t h r e e benzanilides and benzenesulfonanilides tested which have a nitro group in either o f the p a r u positions lie niarkeclly above t h e straight lines of Fig. 1 .
Sept. 5, 1956
RELATIVE BASICITIES OF SELECTED AMIDES
TABLE I EFFECTOF AMIDES ON RATE OF SELF-ETHERIFICATION OF k X 104, m h - 1
98.7 123 125 126 134 176 105 121 126 147 302 107 79.6 81.4 87.9 102 120 156 68.1 74.6 78.4 87.9 107 145 170 59,5 70.8 87.9 145 21.5 33.4 53.2 86.5 13.6 20.2 27.4 40.4 4.79 5.65 7.96 15.5 46.5 44.8 56.2 57.6 68.0 79.4 89.7 108 108
4311
CsHjCOKHR CeHjCOKHCH3 CeHjCOKHCaHs-n CsHjCOSHCaHg-t CsH,CONHCH2CsHb
33.4 39.7 50.0 51.4
Other amides CHs(CHr)aCOIYH2 CHj(CH2)4COS(CH3)2 C6HjCOx( CaHg-n)z CH2CH2CONHCO
3.38 9.08 21.0 72.3
o-C~H~COSHCO
89.1
u
O-CeHdCOCOSH L
152
A
dominantly a t the nitrogen of the un-ionized or a t the oxygen of the ionized form.* An analogous complex for the sulfonamides seems r e a ~ o n a b l e . ~ It is of considerable interest that all of the benzenesulfonamides and most of the chloro- and nitrobenzanilides, in sharp contrast to all of the ketones, esters and ethers of the previous study,3 markedly increased the rate of etherification over that of the blank with no amide present. Although it might a t first glance be considered that these amides are acting simply as acid catalysts, such an interpretation is invalidated by the fact that none of the amides were effective catalysts by themselves. In each determination the benzene solution of benzhydro1 and amide was allowed to reflux for a t least 1 hr. to remove any traces of water before the ptoluenesulfonic acid was added, and etherification never occurred during this period. I n an attempt to elucidate further the characteristics of the accelerating effect the influence, a t two concentrations of p-toluenesulfonic acid, of changing the concentrations of benzenesulfon-pnitroanilide, benz-p-nitroanilide and benzanilide was studied (Table 11). It is evident that doubling the concentration of p-toluenesulfonic acid enhances the accelerating effect of a given amount of either of the nitroamides showing again that they are not functioning simply as acid catalysts. A t both concentrations of p-toluenesulfonic acid, the accelerating effect of the nitroamides is approximately proportional to the amount of amide added while with benzanilide the retarding effect of successive equal portions tends to decrease. If the amount of any of the three amides is held constant doubling the concentration of p-toluenesulfonic acid approximately triples the rate. (8) It has been concluded t h a t amides are not ordinarily enolized t o a significant extent a n d t h a t they are best represented a s t h e resonance hybrid of t h e forms shown in parentheses (L. J. Bellamy, “ T h e Infrared Spectra of Complex Molecules,” John Wiley and Sons, Inc., New York, N. Y., 1954, pp. 175-198). Amides have been shown t o he almost exclusively monomeric in benzene solution a t t h e concentrations used here (M. E. Hohbs a n d W. W. Bates, THIS J O U R N A L , 74, 746 (1952)). Formerly coordination of acids at t h e oxygen of amides was preferred (N. V. Sidgwick, “ T h e Organic Chemistry of Pu’itrogen,” University Press, Oxford, 1942, p. 144), b u t limited recent evidence favors coordination a t t h e nitrogen (S. Mizushima, “Struct u r e of Molecules a n d Internal Rotation,” Academic Press, I n c . , New York, h’. Y., 1954, pp. 118-119). (9) (a) E. A. Fehnel a n d M . Carmack, THISJ O U R N A L , 71, 235 (1949); (h) W. von E. Doering a n d A. K . H o f f m a n , i b i d . , 77, 521 (1956), a n d preceding papers in this series.
Vol. 7s
E. F. PRATT AND J. LASKY
4312
TABLE I1 the push by the corresponding free amide and that EFFECTOF \ 7 ~ THE ~ ~CONCESTRATION r ~ ~ ~ OF CERTAIS the ideal balance is more closely approached as the basicity of the amide decreases.12 AMIDESAT 0.001 AND 0.002 MOLARCONCEXTRATIOSS OF It will be noted (Fig. I) that a change of the p-TOLUESESULFONIC ACID 0 001 mule PTSa Concn. b k X 104, min.-'
0.002 mole PTSa C0ncn.b k X 104, min.
-l
Blanks 0
4 8 16 24
1
98.7
0
293
C~H,SOZX'HC~H,SO~-~~ 146 1 199 2 302 4 393 8
322 365 444 595
CsH,COSHCcH*n'Oyp 116 1 133 2 170 4 8
315 338 378 459
amino group of benzamides to the methylamino group caused an increase in rate. If, as seems probable, the deactivating effect on the p-toluenesulfonic acid is the chief factor to be considered, the steric effects of the methyl group predominate over its electron releasing effect. A further change of the methylamino group to the dimethylamino group, however, caused a decrease in rate and a very striking decrease also resulted when the hydrogen on the nitrogen of ~ - N O ~ C G H ~ C O N H C C~H~SO-Z"C~GH~, H4NOg-p and o-CsH4COCOP\JHwas replaced by a L
I
methyl group (Table I). Since the rate decreasing 8 effect appears only when the last hydrogen on the 16 nitrogen is replaced, it is indicated that these hydrogens in complexes such as I are sufficiently CsHjCOKHC6Hs acidic to catalyze the etherification to a significant extent.13 As noted above these hydrogens in the 16 87.9 16 266 free amide do not catalyze the etherification. 32 78.5 32 226 9change of substituent on the anilino group of 64 02.6 61 199 benzanilides and benzenesulfonanilides (Fig. 1) had 12s 50.0 a greater effect on the rate of etherification than a p-Toluenesulfonic acid. b Unit concentration of amide equals 1/1024 molar; thus a concentration of 16 units equals did a corresponding change on the benzoyl or benthe standard concentration of 1/64 molar. zenesulfonyl group; in fact a change on the benzenesulfonyl group usually had a scarcely signifiThe simplest interpretation which appears to be cant effect. Among the benzanilides the effect of consistent with the foregoing data is that the amides changing both substituents at once was slightly increase the etherification rate by increasing the greater than the sum of the effects of changing one polar character of the benzene medium. In addi- a t a time. I t is of interest that the rates with tion to its function as an acid catalyst the p - benzanilides were closer to those for the sulfontoluenesulfonic acid itself appears to exert a similar anilides than they were to those for the benzeffect since doubling its concentration more than amides of the methylamines and ammonia (Fig. I ) . doubles the rate (Table I1 and reference 3). Rea1change of R in the RCONHCGH~ and CsH5lated effects are frequently encountered in aprotic COXHR amides of Table I from methyl to nsolvents.10 -111 the amides might be expected to butyl or n-amyl causes an increase in rate and a furexert such a rate increasing effect, but it might also ther change to t-butyl produces a larger further inbe expected that with only the least basic amides crease. Again the steric effects of the alkyl groups would it predominate over the above described appear to predominate over their electron releasing catalyst deactivating effect. effects. Ll'ithin the same two groups of amides a The foregoing data also appear to be consistent change of R from n-alkyl to benzyl to phenyl causes with the interpretation that the free amide increases an increase in rate which might be expected from the etherification rate by functioning as a basic both the electronic and steric standpoints. similar catalyst by pushing on the carbon of the benzhy- interpretation appears valid for the results of a drol from which the acid catalyst is pulling the change in R of the RCOXHC6H6 amides froiii hydroxyl group. Evidence in support of such con- mehtyl to chloromethyl to dichloromethyl, but for certed processes for a number of related reactions some unknown reason a further change to trichloroin benzene has been presented.ll Since a detailed methyl did not further increase the rate. analysis of why, with the least basic amides, their I n the last group of amides tabulated it is of ininfluence as basic catalysts predominates over terest that isatin and the isomeric o-phthalimide their influence as deactivators of the acid catalyst, gave markedly different rates, and that of all the while with the most basic amides the reverse is amides tested n-caproamide, a representztive alitrue, would be complicated and perhaps pre- phatic amide, gave the lowest rate. mature, it will not be attempted a t this time. It Experirnentall4 should be noted, however, that as might be expected, the hydrogen on the nitrogen of the coniPreparation and Purification of Materials.- 111 condituplex I, above, appears to be sufficiently acidic to be ents of the reaction mixture were prepared mhere necessary catalytically active (see following paragraph). I t (12) C. G. Swain a n d XI'. P. T,angsdorf, J r , ; b i d . , 73, 2816 (1951), is reasonable to suggest that the maximum etheri- have pointed o u t t h a t steric effects may be extreme T h e steric fication rate is reached only when the proper bal- requirements within a series of pnva-substituted amides such as a r e here, would, however, remain constant. ance exists between the pull by the complex and considered (13) I t is pertinent t o note in this regard t h a t S. Mizushima in 110) Reference 6, pp. 288-290 ( 1 1 ) C. G . Swain a n ? hr 51 Kreevily, 'THIS 1 0 1 ' R N 4 1 , , 77, I122 ( I ' Q ~ z ) ,a n d enrlier imper. f r o m their ~ . : i i x r a t o r ~ - .
t h e hydrogen :iturn '11 t h r S I 3
