Diels-Alder reaction solvent scales

Sulfur dioxide acts as a dienophile ia the Diels-Alder reaction with many dienes (253,254) and this reaction is conducted on a commercial scale with butadiene. The initial adduct, sulfolene [77-79-2] is hydrogenated to a solvent, sulfolane [126-33-0] which is useful for selective extraction of aromatic hydrocarbons from... 

One of the earliest solvent polarity scales is Person s D scale. This scale is based on the endojexo ratio of the Diels-Alder reaction between cyclopentadiene and methyl acrylate (Figure 3.5-2, O = logio endo/exo). This reaction has been conducted in a number of ionic liquids, giving values in the 0.46-0.83 range [26]. 

A warning was given that the 5 molar solution in ether used as a solvent for Diels-Alder reactions would lead to explosions [1], Such a reaction of dimethyl acetylenedicarboxylate and cyclooctatetraene in this solvent exploded very violently on heating. The cyclooctatetraene was blamed, with no supporting evidence [2], It would appear desirable to find the detonability limits of the mixture with ether before any attempt is made to scale up. A safe alternative to lithium perchlorate/ether as a solvent for Diels-Alder reactions is proposed [3],... 

It has been shown that Diels-Alder reactions can be carried out successfully in a range of ionic liquids [12], As highly ordered H-bonding solvents, ionic liquids have the potential for dramatic effects as solvents for such reactions. The range of polarities which can be spanned by varying the cation or anion may be exploited and it has been shown that the endo exo ratio for the reaction between cyclopentadiene and methyl acrylate (Scheme 7.5) is dependent on the polarity of the ionic liquid used [13] (Table 7.2). When the reactions were carried out in a range of ionic liquids, the endo exo values were shown to correlate with the polarity as measured by the Ej scale. 

This explains the experimentally confirmed predictions that polar solvents attenuate the endo-preference, while non-polar solvents increase the cwdo-selectivity of Diels-Alder reactions. The strong correlation between the polarity of the solvent and the endo/exo ratios in the Diels-Alder reaction led to the empirical polarity scale 2 = log endo/exo) using the reaction of cyclopentadiene with methyl acrylate as the standard144. The importance of solvent polarity has also been discerned on the basis of experimental142 and theoretical investigations145. Dependence on the polarizability was also noted146. 

The Use of Solvent Scales to Direct Diels-Alder Reactions... 

The rates, regiochemistry, and stereochemistry of Diels-Alder reactions are affected by the solvent, and are often correlated to solvent polarity scales. In Chapter 15, we will cover orbital interactions that dictate the dominant regio-isomers of Diels-Alder reactions similar to that given below. The diene A is considered to be a nucleophile and... 

Efficient interaction of two or more components occurs if they are combined in a single liquid phase. The Diels-Alder reaction between (2 , 4 )-2,4-hexadien-l-ol and maleic anhydride occurs without solvent as the two components melt together over approximately 3 min [6], This reaction can be performed safely at a 5 mmole scale in a beaker, but doubling the reaction scale or performing the reaction in a smaller vessel causes an extremely exothermic reaction due to the lack of solvent as a heat sink. 

In 2009, Imagawa and Nishizawa reported the first synthesis of ( )-neovibsanin B (63) [46]. They employed an intramolecular Diels-Alder reaction of 91 at 200 °C in dimethyl imidazolidinone (DMI) as a solvent for constructing the core cyclohexenone ring of neovibsanin, leading to a mixture of 92a and 92b (9 1) in 58% yield. DMI plays a cmcial role in accelerating this reaction rate and thus makes it suitable for scale-up. Further manipulation of Diels-Alder adducts 92a and 92b involves introduction of a hydroxymethyl group by Baylis-Hillman reaction with formaldehyde to provide the key intermediate 95, Scheme 11. 

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