4136
J. F. BUNNETT, E. BUNCELBND K. 1;. NAHABEDIAN
to participation of mechanism I11 already presented for amides or to salt effects. All other acids studied yield greater rates than equivalent concentrations of HC104. A plot of log k’ - HO versus log aH20 yields a curve which exhibits a negative w decreasing in magnitude as acidity increases. A straight line is not expected a t low acidities where, according to the above analysis, ha ‘v k 3 / k 2 . At higher acidities the method of analysis overcompensates, due to an additional mode of hydrolysis or salt effects as mentioned before. The effect of salts may be operative through the part they play in B and HB. The variation in effects of salts observed in acetylimidazole hydrolysis may be a more general phenomenon unappreciated because few studies exist of comparable scope on other compounds. Qualitatively the high w = 19.G value of acetylimidazole hydrolysis in perchloric acid is accounted for by mechanism IV. This mechanism predicts the occurrence of oxygen isotope exchange with acetylimidazole a t high acidities. *4reaction scheme similar to mechanism IV was used to account for acid inhibition in thiazoline26a,b
+ H20 + B D + HB D +H B SH+ ~+ B
TH+
D
Z
S
(26) (a) R. B. Martin, S Lowey, E. L. Elson and J. T. Edsall, J . A m . Chem. soc., 81, 5089 (1969). R. B. Martin and A. Parcell, i b i d . , 83, [a) 4830, (b) 4835 (1961). A complete mechanism proposed for thiazoline hydrolysis and acetyl transfer in ref. 27 is unsatisfactory. I n designations similar t o those of ref. 27 we show in a foitbcoming publication
[CONTRIBUTION FROM
THE AXD THE
VOl. s4
and oxazoline2Gc compounds. In the case of some of the thiazoline compounds such as 2-methylthiazoline where the value of k 3 / k s = 0.1 is small, extraordinary powers of the activity of water would be required to account for the decrease in hydrolysis rate by the decrease in water activity. For 2-(l-acetamin0-2-methylpropyl)-thiazoline~~~ and 2-methyloxazoline a value of k3/k2 = 1.2 was obtained, the same as that for acetylimidazole. The identical value for these three compounds is probably coincidental but is nevertheless suspicious and indicates that some common factor, such as a decrease in the activity of water, might account for the results. In such borderline cases it is difficult to assign with certainty the mode of decomposition. By analogy with other thiazoline derivatives26b where k3,/kr = 0.1 to 0.3, the first compound probably decomposes according to mechanism IV. This conclusion is less certain for 2-methyloxazoline. More studies are required on both compounds with a greater variety of acids and salts. Least certain is the mechanism of hydrolysis of acetylimidazole. Even for this compound we favor mechanism I V with the reservations already discussed. Acknowledgments.-The author is indebted to Dr. I$-.P. Jencks for transmissicn of data on the hydrolysis of acetylimidazole in perchloric acid. Thanks are also due to Dr. R. J. P. IVilliams and the Division of General Medical Sciences for their forbearance while this work was performed on a fellowship granted for another pursuit. t h a t a mechanism of t h e following kind is a better representation of all t h e data. (27) R B Martin and R I Hedrick, J A m Chem S o c , 84, 106 (1962).
VENABLECHEMICAL LABORATORY, UNIVERSITY OF NORTHCAROLISA,CHAPELHILL, E.C., METCALF CHEMICAL LABORATORY, BROWNUSIVERSITY, PROVIDEXCE, R. I.]
The Mechanism of Acid-catalyzed Hydrolysis of Azoaryl Ethers1 BY J. F. BUN NETT,^ ERWINBUNCELAND K. V. KAHABEDIAN RECEIVED JULY 13, 1962 The phenolic products of hydrolysis of 4-(~-suIfophenylazo)-l-naphthyl methyl ether (IC) and 4-(p-sulfophenylazo)anisole (11) in oxygen-18-labeled water carry t h e oxygen-18 label in the phenolic hydroxy group. However, 4-(p-sulfopheny1azo)-phenol ( I V ) exchanges oxygen with the medium under the same conditions. Etherification of 4-phenylazo-1-naphtho1 ( I I I a ) and transetherification of 4-phenylazo-1-naphthyl methyl ether ( I a ) are accomplished by refluxing with ethanol under acid catalysis. The kinetics of hydrolysis of I1 in 1-6 M HCIOa solutions have been determined, and w and w * values computed. For several of these reactions a mechanism of nucleophilic displacement a t aromatic carbon is required, and for the rest it seems very likely. The protonated azo linkage is a strong activating group for aromatic nucleophilic substitution.
4-(Phenylazo)-l-naphthylmethyl ether (Ia) and it escaped general recognition. Recent ~ t u d i e s ~ ~ ’ ~ related ethers are exceptionally sensitive to acid- have dealt with the conditions, kinetics and mechcatalyzed hydrolytic cleavage, as represented in anism of such cleavages. eq. 1. Hydrolysis is quite rapid, for example, in Several features of this reaction suggest that i t 0.1 M hydrochloric acid a t 46”. Witt and S ~ h r n i d t , ~differs in kind from ordinary ether cleavage as who discovered this phenomenon in 1892, describe commonly effected by hydrobromic or hydroiodic i t as “gewiss bemerkenswerth.” Although several acid. The reaction occurs readily in dilute acid, other chemists took note of this phenomenon,4-8 it does not require highly nucleophilic anions such (1) This research was supported by t h e National Science Foundation (Grants G-2359 and G-6210). (2) Department of Chemistry, Brown University, Providence, R. I. (3) 0. N. Witt and C . Schmidt, Ber., 25, 1013 (1892). (4) K. H. Meyer, A. Irschick and H. Schlosser, ibid., 47, 1741 (1914). ( 5 ) W. Borsche, W. Muller and C. A. Bodenstein, A n n . , 472, 201 (1929).
(6) K. H. T. Pfister, J . A m . Chem. S o c , 64, 1621 (1932). (7) J. B. Muller, L. Blangey and H. E. Fierz-David, Helo. Chim. Acta, 35, 2579 (1952). (8) V. Ettel, J. Weichet and J. Sparil, Coll. Czech Chem. Comm., 16, 204 (1950). (9) J. F. Bunnett and G. B. Hoey, J . A m . Chem. Soc., 8 0 , 3142 (1968). (10) J. F. Bunnett and E. Buncel, i b i d . . 83, 1117 (19611,
HYDROLYSIS OF A
Nov. 3, 1962
l ETHERS ~ ~
~
&
~ 4137 ~
~
TABLE I OXYGEN-IS TRACER EXPERIRIRNTS
G/>
I
Substrate
-Atom I n the hydrol. medium
yo oxygen-l8----Calcd. for aryl-oxygen Found in lab. prod t h e product ~
0.50 0.4'i,0.47 .4s .45, .41 1.20 .10 116 1.20 . 4.5 .45 .40, .44 IV* 1.20 The product was recrystallized from 1.5774 oxygen-18 enriched water. The product was recrystallized from ordinary water. IC
1.39
11"
It should be noted that all the substrates contain sulfo groups. Therefore the average oxygen18 content expected for complete exchange a t aromatic carbon is, on the assumption that the IV sulfo oxygens do not exchange, less than the oxyas bromide or iodide, and it apparently occurs as gen-I8 content of the solvent water. The assumpeasily with phenyl ethers as with alkyl ethers of tion that sulfo oxygens do not exchange was veria z ~ p h e n o l s . ~In . ~ ~consideration of these facts fied by subjecting azobenzene-4-sulfonic acid to the and the observation that in acetic acid solution the same hydrolytic medium as used with I1 and IV. azoether scission is vitally dependent on the pres- The material isolated after two hours of reflux conence of water, Bunnett and Hoeyg proposed the tained 11.24Yc oxygen-18. This is the normal mechanism of Chart I, in which the actual cleavage abundance (0.2070) within experimental error. is brought about by nucleophilic attack of water on The results in Table I demonstrale that an the aromatic carbon atom. oxygen atom from water of the medium becomes CHARTI attached to aromatic carbon, as called for by the H mechanism of Chart I . However, the fact that azophenol IV exchanges makes these experiments I + H30' X O- & .==I N B O R + HzO indecisive as to whether it is the aryl-oxygen or the alkyl-oxygen bond which is ruptured during the v actual ether cleavage reaction. Kevertheless the results are fully in accord with the mechanism "2"lt of Chart I. H OH," Etherification and Transetherification Studies.I11 + ROH 4- Hf;--f X e k - N a o R The mechanism of Chart I implies that the hydroxy group in azonaphthol I11 should be replaced by an alkoxy group on reaction with an alcohol This mechanism predicts the following conse- under mineral acid catalysis. Such a conversion quences: (1) hydrolysis of azonaphthyl ethers I was in fact described by \Yitt and von Helmoltl* in oxygen-18 labeled water should yield the cor- in 1894. Treatment of 4-(p-tolylazo)-l-naphthol responding naphthols I11 containing the oxygen with zinc chloride and hydrochloric acid in ethanol label; (2) azonaphthols 111 should be trans- afforded 4-(p-tolylazo)-l-naphthylethyl ether in formed into azonaphthyl ethers I by treatment with 80% yield. This method was reported to be supeacidified alcohols; (3) in aqueous alcoholic media of rior to conventional alkylation under alkaline conappropriate composition, states of equilibrium ditions as a preparative method. should prevail between I and 111. The present We found that reaction of 4-phenylazo-lpaper describes such observations. naphthol (IIIa. HC1) with refluxing methanol for The recent kinetic studylo of the hydrolysis of four hours produced the corresponding methyl 4-(p-sulfophenylazo)-l-naphthylmethyl ether (IC) ether Ia in 51% yield. From a similar experiment and of 4-(p-sulfophenylazo)-anisole (11) is now in ethanol solvent, the ethyl ether I b was isolated extended to include the perchloric acid-catalyzed in 76y0vield. hydrolysis of 11. It was also shown that hydrolysis of azonaphthyl ether l a in ca. 10% water:90Yo methanol proceeds Results and Discussion Oxygen Exchange Studies.-For the oxygen-18 only to a state of equilibrium and not to completion. tracer experiments, the hydrolysis of ICin oxygen- The hydrochloric acid concentration was 1.04 M 18 labeled 2 M hydrochloric acid and of TI in and the temperature 46". The reaction was follabeled 4 M hydrochloric acid were carried out. lowed by photometric measurements. Hydrolysis The results of these experiments are shown in the was initially rapid, some 5% of IIIa being produced first three rows of Table I. The last row of Table I in the first five minutes, but i t slowed to a halt a t shows the result obtained when 4- (p-sulfophenyl- about 10% total hydrolysis. The plateau was atazo)-phenol (IV) was subjected to the same hy- tained in 110 minutes; no further hydrolysis occurred in the next 66 hours. drolytic conditions as was 11. Transetherification was also demonstrated to (11) J Haginiwa and I. Murakoshi, J. Pharm Soc Jagan, 73, occur. Azonaphthyl methyl ether I a was trans287 (1953); J. Haginiwa, I . Murakoshi, K. Yokota, H Takayama and TT
i-2
T Tsuchiya, ibid 78, 232 (1958). I
(12) 0. N. Witt and
H.von Helmolt, Bcr., 27, 2351 (1894).
413%
J. F. BUNNETT,E. BUNCELA N D K.
v. T\TAIlSBEDIAN
Vol. 54
TABLE I1 RATESOF HYDROLYSIS OF I1 IN PERCHLORIC ACID SOLUTIONS AT 95.1' log& lwk* [HCIOal,a I\,
104k+,b set.-'
-
log (-h.--) log aE2oc ho
+ 40
log
(
[HCIO
