Polar reaction example

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

The addition proceeds most smoothly with highly functionalized (more polar) steroids as seen in examples by Bernstein and others. The polar reaction conditions pose solubility problems for lipophilic androstane, cholestane and pregnane derivatives. Improved yields can be obtained in some cases by using dimethyl sulfoxide or t-butanol " as solvents and by using sodium A-bromobenzenesulfonamide or l,3-dibromo-5,5-dimethyl hydantoin (available from Arapahoe Chemicals) as a source of positive bromine. The addition of bromo acetate and bromo formate to steroid olefins has been studied to a limited extent. ... 

From empirical observation, ILs tend to be immiscible with non-polar solvents. They can therefore be washed or brought into contact with diethyl ether or hexane to extract non-polar reaction products. Among solvents of greater polarity, esters (ethyl acetate, for example) exhibit variable solubility with ILs, depending on the nature of the IL. Polar or dipolar solvents (including chloroform, acetonitrile, and methanol) appear to be totally miscible with all ILs (excepting tetrachloroaluminate IL and the like, which react). Among notable exceptions, [EMIMJCl and [BMIMJCl are insoluble in dry acetone. 

The reaction is an example of a polar reaction type known as an electrophilic addition reaction and can be understood using the general ideas discussed in the previous section. Let s begin by looking at the two reactants. 

The electrophilic addition of HBr to ethylene is only one example of a polar process there are many others that vve ll study in detail in later chapters. But regardless of the details of individual reactions, all polar reactions take place between an electron-poor site and an electron-rich site and involve the donation of an electron pair from a nucleophile to an electrophile. 

Before beginning a detailed discussion of alkene reactions, let s review briefly some conclusions from the previous chapter. We said in Section 5.5 that alkenes behave as nucleophiles (Lewis bases) in polar reactions. The carbon-carbon double bond is electron-rich and can donate a pair of electrons to an electrophile (Lewis acid), for example, reaction of 2-methylpropene with HBr yields 2-bromo-2-methylpropane. A careful study of this and similar reactions by Christopher Ingold and others in the 1930s led to the generally accepted mechanism shown in Figure 6.7 for electrophilic addition reactions. 

A different picture is observed when a polar radical reacts with a C—H bond of a polar molecule. For example, the reaction of an oxygen atom with the methane C—H bond is characterized by the activation energy of thermoneutral reaction /ic0 54.6 kJ mol-1 and parameter bre= 13.11 (kJ mol-1)172 while the reaction with the methanol C—H bond is characterized by Ed) 50 kJ mol-1 and parameter brc 12.55 (kJ mol-1)172 [30]. For these values of bre, the difference between the activation energies is 4.6 kJ mol-1. The decrease in the activation energy can be explained by the fact that the polar O—H group in the O H C—OH transition state interacts with the O H C polar reaction center. 

An additional polar interaction called multidipole interaction is observed in reactions of peroxyl radicals with polyatomic alcohols [55], A few polar O—H groups interact with the polar reaction center C H O in such systems. A few examples of such interaction are given here [17]. Multidipole interaction sufficiently changes the thermoneutral activation energy of the reaction HOO + alcohol [54] and can be characterized by increment A A E. ... 

Table XV lists the isokinetic temperatures of several reactions representing a wide variety of mechanisms, these examples having been chosen because the isokinetic temperature happened to fall in the popular experimental range between 0 and 100°. There are many other polar reactions that have isokinetic temperatures well outside of the accessible temperature range there are many whose variations in activation energy and entropy are not parallel and these, of course, do not have an isokinetic temperature even approximately. When one of a series of reactions deviates markedly from a parallel trend in activation energy and entropy established by the others, it is probable that it differs in mechanism from the others. This is a better indication of a change in mechanism than either marked differences in rate or in activation energy.

Simple reactivity inversion" implies using an umpoled synthon whose origin has, in principle, nothing in common with the synthon with "unnatural" polarity. An example of this type of reactivity inversion is found in one of the possible synthesis of cw-jasmone (3) in which the nitroethane (4) is used as an equivalent of an "acetyl anion" and reacts with an a,P-unsaturated ketone to give the corresponding 1,4-bifunctional system which can then be transformed by a Nef-type reaction into the dissonant 1,4-dicarbonyl system [5]. An intramolecular aldol condensation finally affords the target molecule (Scheme 5.3). 

As a group the redox reactions are probably least well understood mechanistically. However, one common feature to all redox processes is the involvement of contra-polarization. Selected examples are discussed in this section concerning the effects of polar substituents on redox reactions. 

A related view of the physical basis of the solvent coordinate is the well-known reaction field R, which is the field located on the solute dipole due to the dipole induced solvent polarization. For example, the reaction field for the equilibrated excited state dipole Rlq is given by... 

Ionic or polar reactions of alkyl halides rarely are observed in the vapor phase because the energy required to dissociate a carbon-halogen bond heterolyti-cally is almost prohibitively high. For example, while the heat of dissociation of chloromethane to a methyl radical and a chlorine atom is 84 kcal mole-1 (Table 4-6), dissociation to a methyl cation and a chloride ion requires about 227 kcal mole-1 ... 

We now wish to discuss displacements by nucleophilic reagents (Y ) on alkyl derivatives (RX). These are ionic or polar reactions involving attack by a nucleophile at carbon. A typical example is the reaction of hydroxide ion with bromomethane to displace bromide ion ... 

An example of a polar reaction addition of HBr to ethylene (Section 5.5). 

Ionic liquids have also been used as reaction media (Box 9). The high polarity of quaternary ammonium salts is exploited to favour polar reaction steps. For example, with l- -butyl-3-methylimidazolium tetrafluoborate, 2,7-octadien-l-ol (Section 5.4.3) was obtained in good yield from butadiene and water and was readily separated as it was immiscible with the ionic liquid below 5°C [J. E. L. Dullius, P. A. Z. Suarez, S. Einloft, R. F. deSouza, J. Dupont, J. Fisher and A. DeCian, Organometallics 1998, 17, 815]. 

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