Mechanisms and Orientation in Pyrolytic Eliminations - Eliminations - Introduction - March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th Edition (2013)

March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th Edition (2013)

Part II. Introduction

Chapter 17. Eliminations

17.E. Mechanisms and Orientation in Pyrolytic Eliminations

17.E.i. Mechanisms128

Several types of compound undergo elimination on heating, with no other reagent present. Reactions of this type are often run in the gas phase. The mechanisms are obviously different from those already discussed, since all those require an external base, which may be the solvent, in one of the steps, and there is no external base or solvent present in pyrolytic elimination. Two mechanisms have been found to operate. One involves a cyclic transition state, which may be four, five, or six membered. Examples of each size are

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In this mechanism, the two groups leave at about the same time and bond to each other as they are doing so. The designation is Ei in the Ingold terminology and cyclo-DEDNAn in the IUPAC system. The elimination must be syn and, for the four- and five-membered transition states, the four or five atoms making up the ring must be coplanar. Coplanarity is not required for the six-membered transition state, since there is room for the outside atoms when the leaving atoms are staggered.

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As in the E2 mechanism, it is not necessary that the C–H and C–X bond be broken simultaneously in the transition state. In fact, there is also a spectrum of mechanisms here, ranging from a mechanism in which C–X bond breaking is a good deal more advanced than C–H bond breaking to one in which the extent of bond breaking is virtually identical for the two bonds. Evidence for the existence of the Ei mechanism includes:

1. The kinetics are first order, so only one molecule of the substrate is involved in the reaction (i.e., if one molecule attacked another, the kinetics would be second order in substrate).129

2. Free radical inhibitors do not slow the reactions, so no free radical mechanism is involved.130

3. The mechanism predicts exclusive syn elimination, and this behavior has been found in many cases.131 The evidence is inverse to that for the anti E2 mechanism and generally involves the following facts: (1) an erythro isomer gives a trans-alkene and a threo isomer gives a cis-alkene; (2) the reaction takes place only when a cis β hydrogen is available; (3) if, in a cyclic compound, a cis hydrogen is available on only one side, the elimination goes in that direction. Another piece of evidence involves a pair of steroid molecules. In 3β-acetoxy-(R)-5α-methylsulfinylcholestane (27 shows rings A and B of this compound) and in 3β-acetoxy-(S)-5α-methylsulfinylcholestane (28: rings A and B), the only difference is the configuration of oxygen and methyl about the sulfur. Yet pyrolysis of 27 gave only elimination to the 4-side (86% 4-ene), while 28 gave predominant elimination to the 6-side (65% 5-ene and 20% 4-ene).132 Models show that interference from the 1- and 9-hydrogen atoms causes the two groups on the sulfur to lie in front of it with respect to the rings, rather than behind it. Since the sulfur is a stereogenic center, this means that in 27 the oxygen is near the 4-hydrogen, while in 28 it is near the 6-hydrogen. This experiment is compatible only with syn elimination.133

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4. The img isotope effects for the Cope elimination (17-9) show that both the C–H and C–N bonds have been extensively broken in the transition state.134

5. Some of these reactions have been shown to exhibit negative entropies of activation, indicating that the molecules are more restricted in geometry in the transition state than they are in the starting compound.

Where a pyrolytic elimination lies on the mechanistic spectrum seems to depend mostly on the leaving group. When this is halogen, all available evidence suggests that in the transition state the C–X bond is cleaved to a much greater extent than the C–H bond; that is, there is a considerable amount of carbocation character in the transition state. This observation is in accord with the fact that a completely nonpolar four-membered cyclic transition state violates the Woodward–Hoffmann rules (see the similar case of Reaction 15-63). Evidence for the carbocation-like character of the transition state when halide is the leaving group is that relative rates are in the order I > Br > Cl135(see Sec. 10.G.iii), and that the effects of substituents on reaction rates are in accord with such a transition state.136 Rate ratios for pyrolysis of some alkyl bromides at 320 °C were ethyl bromide, 1; isopropyl bromide, 280; tert-butyl bromide, 78,000. Also, α-phenylethyl bromide had about the same rate as tert-butyl bromide. On the other hand, β-phenylethyl bromide was only slightly faster than ethyl bromide.137 This result indicates that C–Br cleavage was much more important in the transition state than C–H cleavage, since the incipient carbocation was stabilized by a alkyl and α-aryl substitution, while there was no incipient carbanion to be stabilized by β aryl substitution. These substituent effects, as well as those for other groups, are very similar to the effects found for the SN1 mechanism and thus in very good accord with a carbocation-like transition state.

For carboxylic esters, the rate ratios were much smaller,138 although still in the same order, so that this reaction is closer to a pure Ei mechanism, although the transition state still has some carbocationic character. Other evidence for a greater initial C–O cleavage with carboxylic esters is that a series of 1-arylethyl acetates followed σ+ rather than σ, showing carbocationic character at the 1 position.139 The extent of E1 character in the transition state increases in the following order of ester types: acetate < phenylacetate < benzoate < carbamate < carbonate.140 Cleavage of xanthates (Reaction 17-5), cleavage of sulfoxides (Reaction 17-12), the Cope Reaction (17-9), and Reaction 17-8 are probably very close to straight Ei mechanisms.141

The second type of pyrolysis mechanism is completely different and involves free radicals. Initiation occurs by pyrolytic homolytic cleavage. The remaining steps may vary, and a few are shown below. Free radical mechanisms are mostly found in pyrolyses of polyhalides and of primary monohalides,142 although they also have been postulated in pyrolysis of certain carboxylic esters.143 β-Elimination of tosyl radicals is known.144 Much less is known about these mechanisms and we will not consider them further. Free radical eliminations in solution are also known, but are rare.145

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17.E.ii. Orientation in Pyrolytic Eliminations

As in the E1–E2–E1cB mechanistic spectrum, Bredt's rule applies; and if a double bond is present, a conjugated system will be preferred, if sterically possible. Apart from these considerations, the following statements can be made for Ei eliminations:

1. In the absence of considerations mentioned below, orientation is statistical and is determined by the number of β-hydrogen atoms available (therefore Hofmann's rule is followed). For example, sec-butyl acetate gives 55–62% 1-butene and 38–45% 2-butene,146 which is close to the 3:2 distribution predicted by the number of hydrogen atoms available.147

2. A cis β hydrogen is required. Therefore in cyclic systems, if there is a cis hydrogen on only one side, the double bond will go that way. However, when there is a six-membered transition state, this does not necessarily mean that the leaving groups must be cis to each other, since such transition states need not be completely coplanar. If the leaving group is axial, then the hydrogen obviously must be equatorial (and consequently cis to the leaving group), since the transition state cannot be realized when the groups are both axial. But if the leaving group is equatorial, it can form a transition state with a β hydrogen that is either axial (hence, cis) or equatorial (hence, trans). Thus 29, in which the leaving group is most likely axial, does not form a double bond in the direction of the carbethoxyl group, even though that would be conjugated, because there is no equatorial hydrogen on that side. Instead, it gives 100% 30.148 On the other hand, 31, with an equatorial leaving group, gives ~ 50% of each alkene, even though, for elimination to the 1-ene, the leaving group must depart with a trans hydrogen.149

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3. In some cases, especially with cyclic compounds, the more stable alkene forms and Zaitsev's rule applies. For example, menthyl acetate gives 35% of the Hofmann product and 65% of the Zaitsev, even though a cis β hydrogen is present on both sides and the statistical distribution is the other way. A similar result was found for the pyrolysis of menthyl chloride.150

4. There are also steric effects. In some cases the direction of elimination is determined by the need to minimize steric interactions in the transition state or to relieve steric interactions in the ground state.

17.E.iii. 1,4-Conjugate Eliminations151

1,4-eliminations of the type H-C-C=CC-X → C=C-C=C are much rarer than conjugate additions (Chapter 15), but some examples are known.152 One such is the conversion of 32 to 33.153

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