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Kinetics and mechanisms of hydrolysis of cyclic sulphinamidates. Part 2. The breakdown of the intermediate ions formed through the ring opening of 3-phenyl-3,4-dihydro-1,2,3-benzoxathiazin-2-one |
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Journal of the Chemical Society, Perkin Transactions 2,
Volume 1,
Issue 12,
1978,
Page 1211-1214
Pierre Maroni,
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摘要:
1978 1211 Kinetics and Mechanisms of Hydrolysis of Cyclic Sulphinamidates. Part 2.' The Breakdown of the Intermediate Ions formed through the Ring Opening of 3-Phenyl-3,4-dihydro-I ,2,3-benzoxathiazin-2-one By Pierre Maroni," Louis Cazaux, Pierre Tisnes, Maurice Aknin, and Gilbert Sartord, Laboratoire de Synthkse et Physiochimie organique, ERA 686 du CNRS, Universite Paul Sabatier, 118 route de Narbonne, 31077 Toulouse Cedex, France The first step in the ring opening of 3-phenyl-3.4-dihydro-1.2.3-benzoxathiazin-2-one (Ib) is very fast and gives rise to two different intermediate ions depending on the pH of the solutions. Above pH 11, this step proceeds through the cleavage of the ring sulphur-oxygen bondand leadstotheformation of N-(o-hydroxybenzy1)-N-phenyl-sulphinamidate ion (IIb).Below pH 9. the S-N bond is the easiest to break and oc-anilino-o-tolyl hydrogen- sulphite ion (IVb) is obtained. The results for the hydrolysis of sulphinamidate ion (IIb) show that the phenol is much more reactive than the phenolate ion and that the reaction occurs via hydroxide ion attack on the sulphinyl group. Two mechanisms account for the decomposition of the hydrogensulphite ion : (i) in slightly alkaline media (7 < pH < 9). hydroxide ion and base-assisted water attack on the species possessing a non-protonated nitrogen ; (ii) at lower pH, acid attack at the oxygen atom bound to the aromatic ring, concerted with the opening of its bond to the sulphur atom. This mechanism is operative for both species of (IVb), which have similar reactivity.THEhydrolysis of S-phenylperhydro- 1,2,3-oxathiazin-2- one at 70" was reported in Part 1.l In acidic or slightly alkaline media, 3-N-phenylaminopropyl hydrogensul- phite ion (IVa) was obtained; its very slow decomposition to 3-N-phenylaminopropan-1-01(Va) was not investig- ated. In strongly alkaline media, the amino-alcohol (Va) was obtained directly ; however, 3-hydroxypropyl N-phenylsulphinamidate (IIa) an intermediate which did not build up in thc medium, was involved in the reaction mechanism (Scheme 1 of ref. 1). HO PhN 'S' I! 8-, HO NHPh (IYb) 0-As aryl sulphates hydrolyse much more rapidly than their alkylated homologues in acidic solutions, 3-phenyl- 3,4-dihydro-l,2,3-benzoxathiazin-2-one(Ib) was syn-thesised 3 so as to obtain a sufficiently fast transform- ation of the corresponding intermediate (IVb) (see Scheme 1).Moreover the benzo fusion should stabilize the open-chain intermediate ion (IIb) as a phenol function is formed which should delay its decomposition, The ring opening of (Ib) to (IVb) was fast and the breakdown of (IVb) which predominates over the pH range 2--9, could be investigated. Besides, (IIb), which was found Part 1, P. Maroni, M. Calmon, L. Cazaux, P. Tisnhs, G. Sartork, and M. Aknin, preceding paper.J. L. Kiceand J. M. Anderson, J. Amer. Chem. SOC.,1966,88, 5242. to build up in the reaction medium between pH 11 and 14, was the major intermediate in this pH range. Between pH 9 and 11both (IIb) and (IVb) are present and the two hydrolysis reactions compete ; the concentration of each of these species varies as a function of pH, but, as yet, we have been unable to interpret the results.EXPERIMENTAL The kinetics of hydrolysis were followed spectrophoto- metrically by recording at 256 nm the increase in absorb- ance (pH > 4) and at 240 nm the decrease in absorbance (pH -=c3.3) which bothcorrespond to the appearance of the final product. All reactions exhibited good first-order kinetics with respect to the substrates. RESULTS Effect of pH on the Hyddysis of Sulphinamidate lon (IIb) (11 < pH < 14).-The U.V. spectrum of the final product was identical with that of N-o-hydroxybenzylaniline,run at the same concentration, suggesting that the product has this structure.The pH dependence of the U.V. absorbance of (IIb) (pK, ca. 10.2) is the same as that of N-o-hydroxy- benzylaniline. This variation is not consistent with a cyclic sulphinamidate structure which is unable to ionise in this pH range, but is readily explicable in terms of the open- chain N-o-hydroxybenzyl-N-phenylsulphinamidatestruc-ture (IIb) which contains a phenol function; it can be assumed that the N(Yh)SO,- group which is far away from the phenol function, has a negligible effect on its pK,, and the observed value of ca. 10.2 is therefore compatible with this structure. Also, if the ring opening of (Ib) like that of 3-phenyl-perhydro- 1,2,3-oxathiazin-2-one, is assumed to proceed through hydroxide ion attack on the sulphur atom, leading to sulphinamidate ion (IIb), the leaving group would be a phenol for (Ib) whereas it would be an alcohol for (Ia).The rate constant ratio would then be approximately equal to that of the acidity constants, 2.e. 105-106. The expected value of KO= for the hydrolysis of (Ib) (8.43 x low3 x lo51mol-1 s-l, i.e. ca. lo31 mol-1 s-l) would be too large to be measured using conventional techniques. As a matter of fact, kinetic measurements could be carried out, and the rate of hydrolysis was found to be pH independent [hobs 5.0 3 L. Cazaux and P. Tisnbs, J. Heterocyclic Chem., 1976, 13, 665. 1212 x s-l (Table l)]. Therefore, such a rate constant does not pertain to a ring cleavage reaction.So, as opposed to 0 0.3I\01 \0.2 20 40 60 80 100 tls FIGURE Plot of the observed optical density versus time for1 the hydrolysis of 3-phenyl-3,4-dihydro- 1,2, 3-benzoxathiazin- %one (2 < pH < 9; 25'; p 1.0, ICC1) S-phenylperhydro- 1,2,3-oxathiazin-2-one, the hydrolysis was not that of the cyclic compound (ib) but of the open- chain intermediate (Ilb) as shown by the pK,value. All attempts at isolating the intermediate, in particular the use of phase transfer catalysts for its extraction from the reaction medium, failed. The rate constants for the hydrolysis of (IIb) at various pH values are listed in Table 1. J.C.S. Perkin I1 decrease followed by a slower increase, suggesting the appearance and the disappearance of an intermediate.The final product was identified by U.V. and n.m.r. spectros- copy as being N-o-hydroxybenzylaniline: the U.V. spectrum of the hydrolysis product was identical with that of an authentic sample of N-o-hydroxybenzylaniline run at the same concentration. The U.V. spectrum of this intermediate varies with pH, suggesting a protonation-deprotonation equilibrium. Its pK,' value, which was estimated spectro- photometrically to be 4.6, is close to those of the amino function of N-o-hydroxybenzylaniline (4.7) and of the inter- mediate (IVa) (4.8) formed in the course of the hydrolysis of N-phenylperhydro-1,2,3-oxathiazin-2-one.lAn open-chain a-anilino-o-tolyl hydrogensulphite ion structure can thus be considered; as with (IIb)the intermediate (IVb) could not be isolated. Both reactions have pseudo-first-order kinetics, but the first step was very fast and could not be followed long enough for subsequent analysis in every case.The second reaction, corresponding to the absoi bance increase, is the conversion of the intermediate a-anilino-o-tolyl hydro- gensulphite ion (IVb) into N-o-hydroxybenzylaniline (Vb). This second step was not studied for the saturated hetero- cycle (Ia).l In all the buffers investigated general catalysis was important. In acetate buffer, general acid catalysis masked that of hydronium ion, so that, even at low buffer con- centration, the accuracy of the extrapolation to zero buffer concentration was poor. In other pH ranges, the constants TABLE 1 Rate constants for the hydrolysis of N-o-hydroxyhenzyl-N-phenyl sulphinamidate ion (IIb) at 25 "C (p 1 .O, I(C1) 1O3[OH-]/~ 1000 600 250 100 20 10 I) 8 7 5 2 PH 14 13.80 13.40 13 12.30 12 11.95 11.90 11.84 11.70 11.30 Is-1 6 5.4 5.1 5.2 4.61O%"bS 4 + 10gk~,\,~ 1.78 1.73 1.71 1.72 1.66 The deuterium oxide solvent isotope efiect obtained for three different concentrations of NaOH and NaOD (25"; p 1.0, KC1) gave KoH/kon 1.25 0.05.The tliermo-dynamic parameters measured between 25 and 50" yielded \,,\ \ \ \ OL. -L.-10 2FIGURE pH-Rate profile for the hydrolysis of a-anilino-o-tolyl hydrogensulphite ion (IVb) in the absence of buffer (25"; p 1.0, KC1) the following activation parameters: E, 14.6 x lo4 kcal mol-l and AS3 -21 cal mol-l 1C-l.Effect of pH on the Hydrolysis of Hydrogensulphite Ion (IVb) (2 < pH < 9).-In all the buffers investigated, a plot of the optical density against time (Figure 1) exhibits a fast 4.8 5 5.1 4.8 4.8 4.6 1.68 1.70 1.71 1.68 1.68 1.66 k,' for hyclroniunl ion catalysis were easily obtained. A plot of log KO' versus pH is shown in Figure 2: the high level of catalysis observed in acetate buffer prevented an accurate drawing of the junction between pH 3.3 and 4.5. In tris- (hydroxymethy1)aminonlethane buffer, the plot of log h,' versus pH is linear (slope + I), and general base catalysis was observed above pH 7. However, in this buffer, as the pH increases further (pH > 8.5),the catalysis becomes more complex; this can be assigned to a significant involvement of the other open-chain intermediate (IIb).In more acidic solutions (pH < 7), general acid catalysis was observed (Table 2, Figure 3). In monochloroacetate buffer, hydro- TABLE2 Catalytic constants for the hydrolysis of a-anilino-o- tolyl hydrogensulphite ion (IVb) (25'; p 1.0, KC1) kaR/l rno1-I log kBH ~KBH Buffer 12 1.8 x loM2 1.08 -1.75 -1.74 4.80 H,O+ Acetate 6.5 x lo-, -2.19 6.50 Phosphate 2.9 x 10-6 -5.55 15.74 H2O lysis was followed at 14"'because the reaction rates are very high (KB~5.2 x loh21 mol-l 0). DISCUSSION Hydrolysis of Sul$hinamidate Ion (IIb) (11 < pH < 14).-From the conjugate acid-base couple, two possible mechanisms can account for the pH-independent 1978 rate constants (Scheme 2).For hydroxide ion attack (mechanism 1) the rate constant is k,,,, = koH[OH-]aH/ 2 0 2 4 6 8 1012 14 PKT FIGURE3 Bronsted plot of the catalytic constants for the hydrolysis of a-anilino-o-tolyl hydrogensulphite ion (IVb) at 25" (p 1.0, KCl) (KA+ a=); in the pH range under consideration, KA> a~, =giving ?z,,,,~?ZOBKw/KA. Such a mechanism 0 0 9-, HO NHPh '0 NHPh SCHEME2 is consistent with the isotopic effect of 1.25. Thus, making use of the value measured by Bender for the OH -0+0 I 0-isotope effect on KO=, namely koH/kOD= 0.66. This value is in good agreement with the reverse isotope effect expected for nucleophilic hydroxide ion attack. This result, as well as the value of AS (-21 cal mol-l K-l) support a mechanism (Scheme 3) of the same type as the one considered by Bender for the hydrolysis of carb- oxylates and as that put forward 1 for the hydrolysis of 3-pheny1perhydro-lJ2,3-oxathiazin-2-one(Ia)in strongly alkaline media. As for (Ia),l the possibility of aconcerted hydroxide ion attack cannot be excluded.One possible explanation for the large difference in reactivity between the phenolate ion and the phenol with respect to the hydroxide ion could be the existence of a phenolate + so:-8-C HZNHPh OH SCHEME 3 conformation in which the negatively charged group is close to the electrophilic sulphur of the NS0,-group, thus decreasing the reactivity of the sulphur atom and hindering the approach of the hydroxide ion.Water attack (mechanism 2) on the phenolate by intramolecular general base catalysis would lead to KO,,, kHZo[H,O]. For such a mechanism, according to Bruice and Benkovic,' an isotopic effect of 1.8-2.8 is to be expected, which is in disagreement with the observed value of 1.25. Hydrolysis of Hydrogensulphite Ion (IVb) (2< pH fast -9-1 CH2NHPh + Hso; -0 SCHEME4 ionization constant of phenolKA~~o/KAD~O =4.02,and the ratio KWH20/KWD~* 7.5: it is possible to calculate the = 4 M. L. Bender and M. S. Silver, J. Amer. Chem. SOC.,1963,85, 3306. P. Salomaa, Acta Chem.. Scand., 1971, 25, 367. < 9).-In slightly alkaline media (7 < pH < 9), a mechanism for hydroxide ion attack on the sulphinyl M.L. Bender, Ckem. Rev.,1960, 60, 53.' T. C. Bruice and S. J. Benkovic, Bioorganic Mechanisms,' Benjamin, New York, 1966, vol. I, ch. 1, p. 157. 1214 group of the hydrogensulphite function is proposed. This mechanism which operates on the amine form of the substrate, may be a stepwise or a concerted process (Scheme 4). The corresponding rate equation is (1) kobs[St] = k’OJ3[OH-] [st]K’A/(K’A+ GH)+ kB[B][St]K’A/(K’A + aJ1) (1) where [S,] is the total substrate concentration, KA’ the protonation constant of the amine function, KO=’ and kB’ are the constants for base attack on the substrate species possessing a non-protonated nitrogen. Over the pH range considered, KA’ > aH,and equation (1) reduces to (2) with KOH’ 2.9 X lo3 and kB 7 X 10-21 mol-l s-l.Equation (2) is in agreement with the linear relationship (slope + 1) seen in Figure 3 and with the observed gen- eral base catalysis. In acidic media (2 < pH < 7) the low accuracy of the pH-rate profile in acetate buffer makes a thorough dis- cussion difficult. However a mechanism of acid attack at the phenolic oxygen atom O1 concerted with cleavage of the 01-S bond seems likely (Scheme 5). The reaction 0 SCHEME5 would be readier in acidic media if the O1 rather than O2 was protonated, ArOH being a better leaving group than ArO-. Heterolysis of the ArO-S bond should also be, according to the work of Kice and Anderson on sodium aryl sulphates, easier for ArOS0,- than for ArOS0,H.Moreover, if the results of Jencks * for the carbonyl group are extended to hydrogensulphites, general acid catalysis would nut be necessary for the protonation of 02,the resulting ArOS0,H being stable. General acid catalysis would allow, in the case of protonation of 01, the avoidance of the unstable intermediate and the transition state leading to it. This mechanism is described by equation (3) where kH J.C.S. Perkin I1 and kBH are the acid-catalysed rate constants of the N-protonated species of the substrate and kH,o is the kol~[St] = (kHaH + h€z0[H201)[Sb]aH/(KA’ + a,) -t(kH‘aH + kH,O’CH201)[StlKA’/(l~A’ + aH)+ ~BH[BH+][S~~~H/(KA+ GH)+ KBH’TBHf][St]KA’/(KA’ + a,) (3) water-catalysed rate constant; kB’, kBH’, and kH,O’ are the rate constants relative to the non-protonated sub- strate.The value of kH (12 1 mo1-l s-l) is easily computed from the plot of log k,’ uenus pH (Figure 2; pH < 3) ; likewise a value of 2.9 x lo3 1 mol-l s-l is obtained for the constant koH‘ corresponding to the base catalysis mechanism operating above pH 7. The mechanisms put forward in the pH range 2-9 lead to equation (4). k,’ I= (kHaH $-kH20*[&O])aH/(~A’ + a€€)+ (KH‘QI-i + kH20’[H201)Ka’/(KA’+ aH)+ kOEC’[OH-]KA’/(KA’ d-aH) (4) Using the above values of kH and koH’ as well as the spectrophotometrically measured pKA’ (4.61, the agree- ment between the experimental plot (Figure 2) and that calculated from equation (4) is satisfying only if kH’ -kH -1A = 12 1 mol-l s-l and kHZO’-kHBO= B = 2.9 x 1 mol-l s-l.The tu7o species of substrate (IVb) are therefore likely to have similar reactivities leading to klcH-kBH’. The electronic effects of the ionisable amine function (pKA’4.6) are weak since this function is distant from the reaction centre O1. Spatial interactions with the protonated nitrogen atom in pseudocyclic con- formations would only affect the negatively charged oxygen atom O2 without significantly modifying the reactivity or accessibility of the reaction centre O1. Under these conditions, equation (3) becomes (5). kobs = A a~ + B[H,O] -t C[BH+] (5) An intramolecular catalysis involving the anilinium ion, analogous to that reported by Benkovic for salicyl sulphate, would not compete with hydronium ion catalysis significantly, since it would not obey rate equation (5). The slope of the Bronsted plot (Figure 3; 0: 0.33) is in the range given by Jencks8 for concerted mechanisms (0.27-0.45). The value of this slope would obviously be more significant had it been obtained from a greater number of buffer catalytic constants. However, though the points for H,Oi and H,O often deviate from the correlation line, the fact that they are correctly aligned with the buffer datum points suggests that a concerted mechanism is most likely. We thank Dr. 14. Calmon for helpful discussions. [7/1241 Received, 13th JuZy, 19773 W. P. Jencks, Chenz. Rev., 1972, 72, 707. S. J. Benkovic, J. Amer. Chetn. Soc., 1966, 88, 6511.
ISSN:1472-779X
DOI:10.1039/P29780001211
出版商:RSC
年代:1978
数据来源: RSC
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