J.C.S. CHEM. COMM., 1972
`Evidence for a First Order Mechanism in Amide Hydrolysis
`
`525
`
`By J. W. BARNETT and CHARMIAN O'CONNOR*
`(Department of Chemistry, University of Aacckland, Auckland, New Zealand)
`
`Summary Hydrolysis of acetanilide derivatives in con-
`centrated acids is confirmed as an A-1 mechanism by use
`of w and $ parameters.
`
`molecular. Vinnik et al. considered specifically that the
`activated complex incorporated the protonated substrate
`and a sulphuric acid molecule.
`We now report that the phenomenon of increasing rate in
`concentrated acid media occurs for a large number of sub-
`AMIDES generally exhibit a maximum in their hydrolysis
`stituted acetanilides (I) undergoing hydrolysis in sulphuric
`rate profiles at moderate acidity,l and in the case of some
`acid, and in an extreme case in perchloric acid also. For
`nitro-derivatives of acetanilide this is followed by a local
`
`w/w sulphuric a ~ i d . ~ ~ ~ We
`minimum at ca. 70-75%
`those substrates where the rate increases were sufficiently
`recently reported4 this phenomenon in the hydrolysis of N-
`large over an adequate range of acidity, to justify
`mathematical analysis, we have tested the data using the
`acetylsulphanilic acid in sulphuric acid. On the basis of
`
`TABLE
`Typical rate data for hydrolysis of substituted acetanilides in concenkated acid media and analysis of the data
`by use of Bunnett w and Bunnett-Olsen linear free energy velationships.
`Temp. ("C)
`Position of substituenta
`1 0 5 ~ ~
`(s-1)
`% 4 w H W 4
`3
`4
`5
`80.0
`96.6
`
`2
`
`6
`
`99.6
`14.2
`52.0
`7.36
`30.9
`5.03
`15.5
`2.09
`6.43
`1.78
`1.12
`0.499
`2-47
`0-930
`1.44
`0-574
`1.55
`4-09
`11.9
`2.29
`297
`44-5
`4-31
`-0.905
`578
`258
`13.9b
`0-233b
`16.7P
`1-50b
`yo w/w HC10,
`70.0
`50.0
`
`128
`30.6
`
`551
`<0.1
`
`Br
`
`Br
`
`W
`
`- 0.48
`- 0.52
`- 0.43
`- 0.49
`- 0.34
`
`-0.51
`- 0.44
`- 0-2 1
`- 0.48
`
`9
`
`- 0.39
`-0.41 - 0.38
`- 0.40
`- 0.26
`
`- 0.45 - 0.37
`
`-0.15
`
`-0 -47
`
`- 0.52
`
`-0.16
`
`100.0
`95.3
`90.0
`80.3
`80.0
`100.0
`105.0
`100.0
`105.0
`100.0
`100.0
`100.0
`100.0
`55.0
`65.0
`
`SO,H
`Br
`
`OH
`
`NO,
`
`SO,H
`SO,H
`SO,H
`SO,H
`SO,H
`c1
`c1
`Br
`Br
`I
`SO,H
`CH,
`Br
`NO2
`
`Br
`Br
`100.0
`NO2
`NO2
`25.0
`a Substituent is H unless stated otherwise;
`
`NHCOMe
`I
`
`b interpolated from ref. 2; C interpolated from ref. 3(b).
`
`Bunnett w 5 and Bunnett-Olsen linear free energys relation-
`ships (see Table). In all cases correlation coefficients were
`good (generally better than 0.99). The values of w all lie
`in the range -2.5 to 0.0 and the values of 4 are all negative
`(although some are <-0.34,
`the original limit of values
`found by Bunnett and OlsenO) and thus they are character-
`istic of reactions in which water is not involved in the rate
`determining step. These results record the first application
`of w and C$ values to an A-1 mechanism for amide hydrolysis.
`
`(Received, 28th February 1972; com. 333.)
`
`increasing values of activation energy over this region of
`increasing rate, the mechanism of hydrolysis was inter-
`preted2p 3 s 4 as having changed from bimolecular to uni-
`
`1C. J. O'Connor, Q2uart. Rev., 1970, 24, 553.
`2 J. A. Duffy and J. A. Leisten, J . Chem. SOL, 1960, 853.
`3 (a) M. I. Vinnik, I. M. Medvetskaya, L. R. Andreeva, and A. E. Tiger, Buss. J . Phys. Chem., 1967, 41, 138; (b) M. I. Vinnik and
`I. M. Medvetskaya, ibid., p. 947.
`4 J. W. Barnett and C. J. O'Connor, Tetrahedron Letters, 1971, 2161.
`6 J. F. Bunnett, J . Amer. Chem. Soc., 1961, 83, 4956; 4968; 4973; 4978.
`6 J. F. Bunnett and F. Olsen, Canad. J. Chem., 1966, 44, 1899; 1917.
`
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`
`Published on 01 January 1972 on http://pubs.rsc.org | doi:10.1039/C39720000525
`
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