ContentsI. Introduction 3505 II. Thioesters 3506 A. Thioalkanoates 3506 B. Thiobenzoates 3510 III. Thiocarbonates 3512 IV. Isothiocyanates 3516 V. Thioaldehydes and Thioketones 3517 VI. Thioamides and Thioureas 3517 VII. Thiocarbamates 3519 VIII. Halogenothioformates and Related Compounds 3520 IX. Conclusions 3522 X. Acknowledgments 3523 XI. References 3523 † In this review, the generic terms thioesters, thiocarbonates, thiocarbamates, and halogenothioformates will be used to comprise the corresponding thiol, thiono, and dithio derivatives.
Second-order rate constants (fcN) for the nucleophilic reactions of piperidine, morpholine, piperazine, and N-substituted piperazines with the title substrates are reported in water, at 25 °C, ionic strength 0.2 M (maintained with KC1). The Bronsted-type plot obtained for the aminolysis of phenyl thiolacetate is linear while that for the p-nitrophenyl derivative (NPTA) is curved, with the center of curvature at pK" = 10.5 (pKa°). According to these results the most likely mechanism involves a zwitterionic tetrahedral intermediate (T*), for which decomposition to products is the rate-limiting step for all the reactions, except that of NPTA with piperidine. For this reaction the formation of T* is rate determining. A semiempirical equation based on the above hypothesis accounts for the Bronsted-type curve obtained in the aminolysis of NPTA. Estimation of the microscopic rate constants involved, in a possible more general reaction scheme and evaluation of the -,'ß of T* indicate that expulsion of the leaving group of the substrate from T* is faster than deprotonation of T* by a base, precluding therefore the formation of an anionic tetrahedral intermediate. The fact that pEa°= 10.5 for the NPTA reactions means that an (hypothetical) amine of pEa = 10.5 leaves T* as readily as p-nitrothiophenoxide ion (pKa = 4.6). From these and other data it is calculated that the nucleofugality from T* of an amine of pK" = 4.6 is ca. 3 X 104 times larger than that of p-nitrothiophenoxide ion. The estimated pAa°v alues for the aminolysis of (hypothetical) aryl acetates with leaving groups of pKa = 4.6 and 6.5 (the same pKh as thiophenol) are pKa°= 8.0 and 9.0, respectively, which gives nucleofugality ratios (a given amine/aryl oxide ion) from the oxy T* smaller than those from the corresponding sulfur T*. It is claimed that expulsion of ArS-from T* is only slightly slower than that of an isobasic ArO" from the oxy T*. Therefore, the above results indicate that the "push" provided by ArS in T* to expel a given amine is much stronger than that exerted by an isobasic ArO in the oxy T*. Activation parameters are reported for the reactions of the title substrates with piperidine, piperazine, and N-formylpiperazine.
The leaving abilities of pyridines and phenolates from a tetrahedral intermediate formed in the reactions of 2,4-dinitrophenyl methyl carbonate with 3-and 4-substituted pyridines are quantitatively compared through a curved Brqnsted plot obtained from these nucleophilic reactions. Curvature is explained through a tetrahedral intermediate and a change in ratedetermining step from its breakdown to its formation as the basicity of the nucleophile increases; a semiempirical equation reported based on these assumptions gives account of the experimental results. Curvature, centered at pK, -7.8, shows that 2,4-dinitrophenolate (pK, -4) has the same leaving ability as a pyridine of pK, -7.8, i t . , pyridines seem to be ca. lo4 times better leaving groups from a tetrahedral intermediate than phenolates of the same basicity.Leaving abilities of nitrogen and oxygen bases from tetrahedral intermediates can be evaluated from curved Brfnsted plots obtained in nucleophilic reactions, but quantification has been difficult owing to scatter of points in the plots arising from dissimilar nucleophiles employed.' 3-and 4-substituted pyridines offer the advantage of a homogeneous series with a wide range of pK, values, which has proved useful in quantitative interpretation of curved Brfnsted T h e present paper reports a quantitative evaluation of the relative leaving abilities between pyridines and 2,4-dinitrophenolate from the tetrahedral intermediate formed in the nucleophilic reactions of 2,4-dinitrophenyl methyl carbonate with a series of 3-and 4-substituted pyridines (eq 1). OCH, Experimental Section2,4-Dinitrophenyl methyl carbonate was prepared according to Pianka,4 mp 87 "C (lit.4 87-88 "C), and identified by N M R spectroscopy. Nicotinamide, p.a., Merck, was used directly. The rest of the pyridines and reagents were purified as previously de~cribed.~ Reactions were followed measuring the increase in 2,4-dinitrophenolate or the corresponding phenol absorbance by means of a Pye-Unicam S P 1800 spectrophotometer. Two to four pH values and several concentrations of total base were used (see Table I). Temperature was kept at 25 f 0.1 "C and the ionic strength adjusted to 0.2 M with NaC104. Good pseudo-first-order rate constants ( k o b s d ) were obtained by the "infinity" method (at least 20-fold excess of total base over substrate was used). Reactions were followed for at least 3 half-lives and infinity absorbance values taken after 8-10 halflives.2,4-Dinitrophenolate was identified as a stable product of the reactions by comparison of its UV spectra with those of authentic samples. The existence of a methoxycarbonylpyridinium intermediate was inferred from the observation of a decrease in absorbance of the spectra obtained by repetitive scanning between 270 and 400 nm, after completion of the reactions of 2,4-dinitrophenyl methyl carbonate with 4-dimethylamino-and 4-methylpyridines under conditions such that the formation of the intermediate was faster than its hydrolysis. The rate constants for hydrolysis of these substitute...
The rate constants for nucleophilic reaction of nine substituted pyridines with methyl chloroformate gives a sharply curved Bronsted plot, the slope changing from p 0.93 to 0.1 5 with increasing reactivity. This contrasts with the straight line (p 0.93) observed with p-nitrophenyl acetate, and is shown to be quantitatively consistent with a change in rate-determining step. It is argued that this is from breakdown to formation of a zwitterionic tetrahedral intermediate which is only just stable enough to exist. The hydrolytic stabilities of some of the rnethoxycarbonylpyridinium ions produced by this reaction, and the nucleophilic reactivities towards methyl chloroformate of imidazole, of phenolate, p-nitrophenolate. and acetate anions, and of phosphate dianion are reported and discussed.
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