Diels-Alder reactions pressure effects

The observation that the transition state volumes in many Diels-Alder reactions are product-like, has been regarded as an indication of a concerted mechanism. In order to test this hypothesis and to gain further insight into the often more complex mechanism of Diels-Alder reactions, the effect of pressure on competing [4 + 2] and [2 + 2] or [4 + 4] cycloadditions has been investigated. In competitive reactions the difference between the activation volumes, and hence the transition state volumes, is derived directly from the pressure dependence of the product ratio, [4 + 2]/[2 + 2]p = [4 + 2]/[2 + 2]p=i exp —< AF (p — 1)/RT. All [2 + 2] or [4 + 4] cycloadditions listed in Tables 3 and 4 doubtlessly occur in two steps via diradical intermediates and can therefore be used as internal standards of activation volumes expected for stepwise processes. Thus, a relatively simple measurement of the pressure dependence of the product ratio can give important information about the mechanism of Diels-Alder reactions. 

Alternatively, authors have repeatedly invoked the internal pressure of water as an explanation of the rate enhancements of Diels-Alder reactions in this solvent ". They were probably inspired by the well known large effects of the external pressure " on rates of cycloadditions. However, the internal pressure of water is very low and offers no valid explanation for its effect on the Diels-Alder reaction. The internal pressure is defined as the energy required to bring about an infinitesimal change in the volume of the solvents at constant temperature pi = (r)E / Due to the open and... 

Tire importance of hydrophobic interactions in the aqueous acceleration is further demonstrated by a qualitative study described by Jenner on the effect of pressure on Diels-Alder reactions in water and a number of organic solvents. Invariably, the reactions in water were less accelerated by pressure than those in organic solvents, which is in line with the notion that pressure diminishes hydrophobic interactions. 

Mechanistic studies have tried to unravel the origin of the special effect of water. Some authors erroneously have held aggregation phenomena responsible for the observed acceleration, whereas others have hinted at effects due to the internal pressure. However, detailed studies have identified two other effects that govern the rate of Diels-Alder reactions in water. 

Heteroatom functionalized terpene resins are also utilized in hot melt adhesive and ink appHcations. Diels-Alder reaction of terpenic dienes or trienes with acrylates, methacrylates, or other a, P-unsaturated esters of polyhydric alcohols has been shown to yield resins with superior pressure sensitive adhesive properties relative to petroleum and unmodified polyterpene resins (107). Limonene—phenol resins, produced by the BF etherate-catalyzed condensation of 1.4—2.0 moles of limonene with 1.0 mole of phenol have been shown to impart improved tack, elongation, and tensile strength to ethylene—vinyl acetate and ethylene—methyl acrylate-based hot melt adhesive systems (108). Terpene polyol ethers have been shown to be particularly effective tackifiers in pressure sensitive adhesive appHcations (109). 

The Diels-Alder reaction is the most widely used carbon-carbon, carbon-heteroatom and heteroatom-heteroatom bond-forming reaction for the construction of six-membered rings therefore it is not surprising that many methods have been used to accelerate the reaction and to improve its selectivity. Chapters 2, 3 and 5 illustrate the effects of temperature, Lewis acids and pressure, respectively this chapter provides a survey of other physical and chemical methods by which the Diels-Alder reaction can be profitably carried out. 

Whereas maleic anhydride can react with furan (139a) at ambient pressure, citraconic anhydride (140) reacts only at high pressures due to the strong deactivating effect of the methyl group (Schemes 5.21 and 5.22). The two-step synthesis [53] of the palasonin (141), in an overall yield of 96 %, is a good example of the acceleration of the Diels-Alder by high pressure (Scheme 5.21). Previous synthesis [54] based on the thermal Diels-Alder reaction of furan with methoxy carbonyl maleic anhydride required 12 steps. 

Intermolecular befera-Diels-Alder reactions of enamino ketones with highly substituted vinyl ethers. Effect of high pressure on the kinetics and diastereoselectivity [77]... 

The Diels-Alder reaction can be greatly enhanced by high pressure (Chapter 5) but the effect of pressure is generally weaker in aqueous medium than in organic solvent. Results of high pressure-mediated Diels-Alder reactions of furans and acrylates in water and dichloromethane are reported in Table 6.6 [32]. In aqueous medium the cycloadditions occur with lower yields and less diastereoselectivity than in dichloromethane and, in some cases, addition-substitution reactions were observed. 

The effect of pressure on the rate constant of the Diels-Alder reaction between maleic anhydride and isoprene was investigated in SC-CO2 at 35 °C and at pressures ranging from 90 to 193 bar. For comparison purposes, the reaction was also carried out in an apolar solvent such as propane under... 

A systematic study of the effect of pressure and density on the regiochemical course of the Diels-Alder reactions of methyl acrylate and 2-substituted 1,3-butadienes carried out in SC-CO2 was recently reported [87]. The reactions were compared with those carried out in a conventional medium such as toluene. Some results are illustrated in Table 6.15. 

Many Diels-Alder [4 + 2] cycloadditions show a powerful pressure-induced acceleration, which is often turned to good synthetic purpose as discussed in Section III.A.2. Table 1 illustrates the effect of pressure on the Diels-Alder reaction of isoprene with acrylonitrile as a representative example. This reaction is accelerated by a factor of 1650 by raising the pressure from 1 bar to 10 kbar28. 

In Scheme 14 the effect of pressure on Diels-Alder reactions with acyclic heterodienophiles or heterodienes is presented. The application of high pressure leads also in these reactions to an enhancement of rates and improvement of yields. The hetero-Diels-Alder reaction (entry 3) is a good example of the interplay between pressure and temperature. At high pressure the rate of reaction as well as the diastereoselectivity are increased. The pressure-induced acceleration allows the temperature of reaction to be lowered, which leads to a further increase of diastereoselectivity. 

Whilst it is obviously valuable to measure the solubility of reagents in the SCF, it is important to be aware that the solubility in a multicomponent system can be very different from that in the fluid alone. It is also important to note that the addition of reagents and catalysts can have a profound effect on the critical parameters of the mixture. Indeed, at high concentrations of reactants, the mole fraction of C02 is necessarily lower and it may not be possible to achieve a supercritical phase at the temperature of interest. Increases in pressure (i.e. further additions of C02) could yield a single liquid phase (which would have a much lower compressibility than scC02). For example, the Diels-Alder reaction (see Chapter 7) between 2-methyl-1,3-butadiene and maleic anydride has been carried out a pressure of 74.5 bar and a temperature of 50 °C, assuming that this would be under supercritical conditions as it would if it were pure C02. However, the critical parameters calculated for this system are a pressure of 77.4bar and a temperature of 123.2 °C, far in excess of those used [41]. 

While many observations are well understood, e.g. those dealing with the reaction rate or with the selectivity, there are some factors which cannot be generalized. Many transformations of particular reactants or under unusual reaction conditions led to unexpected results. There are often singular explanations for such reactions but no overall concept. For instance, computations on Diels-Alder transition structures and thermodynamics of retro-Diels-Alder reactions confirmed that the activation volume of these [4 + 2]-cycloadditions is negative80. This result, pointing to the compact character of the transition structure, is used to explain the dependence of reactivity and selectivity on internal as well as external pressure81-83. These effects are only observed at relatively high external pressures (Table 5). 

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