Esters that have only one a-hydrogen atom do not undergo acetoacetic ester condensation. Triphenylmethylsodium, mesitylmagnesium bromide, sodium amide can do This. Fl-diketones are fairly readily cleaved by bases.
Esters that have only one a-hydrogen atom do not undergo acetoacetic ester condensation. Triphenylmethylsodium, mesitylmagnesium bromide, sodium amide can do This. Fl-diketones are fairly readily cleaved by bases.
Esters that have only one a-hydrogen atom do not undergo acetoacetic ester condensation. Triphenylmethylsodium, mesitylmagnesium bromide, sodium amide can do This. Fl-diketones are fairly readily cleaved by bases.
starting material. In fact, esters that have only one a-hydrogen atom do not undergo the acetoacetic ester condensation in the presence of sodium alkoxidc catalysts, because the fl-keto ester formed would not be sufficiently acidic to be transformed to its conjugate base to any signifi- cant extent. The equilibrium in such reactions, however, may be forced to the right by the use of more strongly basic catalysts. Triphenyl- methylsodium, mesitylmagnesium bromide, sodium amide, and diiSO- propylaminomagnesium bromide arc among the bases that have been found capable of bringing about the formation of fl-keto esters that con- tain no a-hydrogen atoms. u.u 13-3b. Alkaline Cleavage of fl-Diketones and Related Compounds. In general, compounds of the type RCOX may be easily cleaved by alkali if X 6 is a fairly stable anion (cf. the alkaline hydrolysis of esters). It is therefore not unexpected that fl-diketones are fairly readily cleaved by bases. Pearson and Sandy studied the cleavage of acetylacetone by sodium ethoxide in ethanoL 17 They made the observation, surprising at first glance, that the reaction is of the first order, its rate being propor- tional to the concentration of the reactant present in the smaller con- centration. This observation is quite rational, however, in vi ew of the following reaction mechanism: e e CH,COCHsCOCHa + EtO CH,COCHCOCH, + EtOH e 0 0 0 0 + EtO 8
6Et e -> CH,CO,Et + CH,COCH, e e CH,COCHa + EtOH-> CH,COCH, + EtO If we assume that the rate-controlling step is the decomposition of the acetylacetone-ethoxide-ion adduct and that all the other steps are rela- tively fast, we can derive the kinetic equation v = k[CH3COCH.COCH,][EtO- ] However, if the acid-base equilibrium of the first equation is established rapidly, [CHaCOCH.COCH,][EtO- ] = Therefore v = (13-2) "C. R. Hauser et al., J . Am. Chern. Soc., 68,2647 (1946); 69, 2649 (1947); 71, 1350 (1949). ., R. G. Pearson and A. C. Sandy, J . Am. Chem. Soc., 73,931 (1951). I c-c BOND FORMATION AND CLEAVAGE IN RC02H DERivATIVES 315 Acetylacetone is an acid of such a strength that the concentration of its anion present in a basic solution will be essentially equal to the concentra- tion of sodium ethoxide or of acetylacetone added, depending on which is the limiting reagent. The mechanism given, then, explains the observa- tion of first-order kinetics. The alkaline ethanolysis of phenacylpyridin- ium ions follows a similar kinetic equation and has the same type of mechanism. 17 The alkaline hydrolysis of acetylacetone is a more complicated reac- tion, the kinetic equation having the form of (13-2) with an additional term involving hydroxide ion. 11 v = + The first term corresponds to cleavage by a mechanism like that followed in alcoholic solution. As Pearson and Mayerle point out, the second term, involving an additional hydroxide ion, is probably due to cleavage by the mechanism e e 0 .0 I oH- I e e ===' CHaCCH,COCHa-+ CHaCO. + CH.COCHa 6H 6e Although the doubly charged intermediate must be present at a much smaller concentration than the singly charged one, its specific rate con- stant for cleavage is probably much larger. This situation is somewhat similar to that found in the Cannizzaro reaction (Sec. ll-4a). Dimethylacetylacetone cannot' be "protected" by transformation to its conjugate base and is therefore cleaved much more rapidly than the unsubstitute<I compound or its monomethyl derivative. 0 II CH,CC(CH,).COCH, + OH- ...... CH,CO.- + (CH,).CHCOCH, The kinetics in this case are second-order, first-order in hydroxide ion and first-order in ketone. 18 The study of the basic cleavage of chloral hydrate carried out by Gustafsson and Johanson showed that this part of the haloform reaction probably has a mechanism of the type described for the cleavage of fl-diketones. 11 This mechanism should be modified to agree with the observation of general base catalysis," and, indeed, it is possible that the reactions studied by Pearson and coworkers are also subject to general base catalysis. 13 R. G. Pearson and E. A. Maycrl c, J . A m. hem. Soc., 73,926 (1951) . 10 C. Gustaf880n and M. Johanson, A eta Chern . Scand., 2, 42 (1948). 316 PHYSICAL ORGANIC CHEMISTRY . PROBLEMS . I. Suggest a mechaniam to explain why potassium cyanide is a catal m the tranaformatlon of RCOC0 2 H to RCHO. yst 2. a plau.sible mechanism for the reaction of threonine (CH,CHOHCHNH,_ CO,H) wtth and aluminum iona. The products include conaiderable acetaldehyde and g)ycme and less a-ketobutyric acid and ammonia . . 3. equilibrium c?nstants, as in the explanation in Sec. 13-3a, explain how the mued Clll.lBen condensatiOn of ethyl benzoate with ethyl isobutyrate is driven to th right by the use of triphenylmethylsodium. e 4. Suggest a reasonable mechaniam for the alkaline cleavage (general base-eata.- lyzed) of chloral hydrate to chloroform and formate iona. Chapter }4. REARRANGEMENTS DUE TO ELECTRON-DEFICIENT CARBON Several types of rearrangement reactions have already been described under various other headings. The Stevens rearrangement has been mentioned as an example of an SNi reaction (Sec. 6-3); allylic rearrange- ments by the SNl and SN2' mechanisms were discussed in Sec. 6-5; and the Favorskii rearrangement in Sec. l0-3c. Other carbon-skeleton rearrangements will be discussed here. 14.-1. Carbonium-ion Rearrangements. Of the very large number of carbonium-ion rearrangements we shall discuss only a few, most of them chosen because of the care with which they have been studied. It is hoped, nevertheless, that certain generalizations pointed out in this and subsequent sections will lead to an understanding of the nature of most of the rearrangements not mentioned specifically. 14-la. Evidence that Carbonium Ions Are Intermediates. Meerwein and van Ernster obtained some of the first strong evidence that car- bonium ions may be intermediates in carbon-skeleton rearrangements in their study of the rearrangement of camphene hydrochloride to iso- bornyl chloride. They observed that the reaction rate increased with the nature of the solvent in roughly the same order that had been found for the ability of solvents to ionize triphenylmethyl chloride. They further established that compounds such as HgCh, FeCI,, SnCI., etc., capable of coordinating with a chloride ion, were excellent catalysts for the reaction. ft was later shown that the rearrangement of the chloride was slower than that of the bromide or arylsulfonate but faster than that of the trichloroacetate or m-nitrobenzoate.' This order of reactivity is understandable, since the ease of ionization should increase with the stability of the anion being formed. The probability of a carbonium-ion mechanism for rearrangement reactions was emphasized (in somewhat different language) by Whitmore 1 H. Meerwein and K. van Emster, Btr., 55, 2500 (1922) . 1 H. Meerwein, 0 . Hammel, A. Serini, nnd J . Vorster, Ann., 453, 16 (1927). 31 7
Physical Organic Chemistry — 3: Plenary Lectures Presented at the Third IUPAC Conference on Physical Organic Chemistry, Montpellier, France, 6 - 10 September, 1976
Physical Organic Chemistry—Ii: Specially Invited Lectures Presented at the Second IUPAC Conference on Physical Organic Chemistry Held at Noordwijkerhout, Netherlands, 29 April–2 May 1974