Polar aprotic solvents, reverse

Benzo-l,2,3-triazin-4-ones with the general structure 6.54 (X = O, S, or H2) are obtained by diazotization of the appropriate aniline derivatives 6.53 (Scheme 6-38). In polar aprotic solvents (e. g., nitrobenzene) the reverse reaction takes place to give the diazonium ion (for an example see Kullick, 1966). Diazotization of 1,8-diamino-naphthalene yields l-i/-naphthol[l,8-cfe]triazine (6.55 Tavs et al., 1967). In concentrated HC1 the triazine ring is opened again. 

Problem 7.8 Explain why the order of reactivity of Problem 7.7(c) is observed in nonpolar, weakly polar aprotic, and polar protic solvents, but is reversed in polar aprotic solvents. 

SN1 versus S There are two different mechanisms involved in the nucleophilic substitution of alkyl halides. When polar aprotic solvents are used, the SN2 mechanism is preferred. Primary alkyl halides react more quickly than secondary alkyl halides, with tertiary alkyl halides hardly reacting at all. Under protic solvent conditions with non-basic nucleophiles (e.g. dissolving the alkyl halide in water or alcohol), the SN1 mechanism is preferred and the order of reactivity is reversed. Tertiary alkyl halides are more reactive than secondary alkyl halides and primary alkyl halides do not react at all. 

While the addition/oxidation and the addition/protonation procedures are successful with ester enolates as well as more reactive carbon nucleophiles, the addition/acylation procedure requires more reactive anions and the addition of a polar aprotic solvent (HMPA has been used) to disfavor reversal of anion addition. Under these conditions, cyano-stabilized anions and ester enolates fail (simple alkylation of the carbanion), but cyanohydrin acetal anions are successful. The addition of a cyanohydrin acetal anion to l,4-dimethoxynaphthalene-Cr(CO)3 occnrs by kinetic control at C-/3 in THF/HMPA and leads to the O -diacetyl derivative after methyl iodide addition and hydrolysis of the cyanohydrin acetal. Monoacylation of 1,4-dimethoxynaphthalene-Cr(CO)3 has been achieved nsing the seqnence of reactions shown in eqnation (126). ... 

Many synthetic problems requiring a reverse in the traditional mode of selectivity have been solved by the application of these and other polyanions. It is worthwhile to note that this novel aspect of carbanion utilization was brought to light owing to the elaboration of the conditions (strong bases, polar aprotic solvents) which secured completeness in carbanionic species generation. 

We have learned that nucleophilicity depends on the solvent when nucleophiles of very different size are compared. For example, in polar protic solvents nucleophilicity follows the trend F < OF < Br < I", but the reverse is true in polar aprotic solvents. Predict the trend in nucleophilicity for these halide anions in the gas phase, with no solvent. 

Reduction of 9-substituted anthracenes, (91), leads to radical anions, which, because of the electron-withdrawing substituents, are quite stable with respect to protonation and cleavage in aprotic solvents. In polar aprotic solvents the radical anions exclusively dimerize, and the reaction has been the subject of a number of studies [247-258]. The products are the tail-to-tail dimeric dianions as in Eq. (57), which are fairly stable. In CV the dimer dianions can be detected as a new oxidation peak on the reverse scan at a potential several hundred millivolts anodic relative to the potential of radical anion formation. On preparative or semipreparative scales the dimer dianion has in a single case been detected by H-NMR [249], and oxidative electrolysis of the dimer dianions in most cases restores the starting material. 

In addition to regiochemistry, acyclic carbonyl compounds can produce two possible stereoisomeric enolates, E or Z, as shown above. Steric interactions determine the favored enolate stereochemistry. Under reversible conditions, Z enolates are more stable than E as they minimize steric interactions, especially if R is large. Z enolates are also usually favored under irreversible conditions in polar aprotic solvents like HMPA that complex cations well and break up ion pairing, effectively reducing the bulk around the oxygen anion. Under irreversible conditions in ether solvents, the E enolate is often favored because the steric size of the base/cation aggregate around the oxygen dominates, especially if R is smaller, as with esters. 

Repeating this experiment in the presence of the polar aprotic solvent, HMPA, reversed the stereoselection in the ring closure. 

Stable, homogeneous solutions of the corresponding radical anions as shown in Equation 7.6 [4, 48], Radical anions can be formed efficiently only in polar aprotic solvents such as THE and glymes. Aromatic radical anions such as sodium naphthalene react with monomers such as styrene by reversible electron transfer to form the corresponding monomer radical anions as shown in Scheme 7.5 (R = H). 

Radical Anions Many aromatic hydrocarbons react reversibly with alkali metals in polar aprotic solvents to form... 

Inositols and Other Cyclohexane Derivatives - The isoxazolidinocarbocyclic derivative 89 has been produced together with a five-membered carbocyclic compound (diagram 72 in Section 2.1) by cycloaddition from nitrone 73. The formation of 89 predominated in polar protic solvents whilst the reverse was observed in non polar and polar aprotic solvents. 

The same order is found in other protic solvents. This is also the order expected on the basis of polarizability the larger and more polarizable anions should be the most nucleophilic. In polar aprotic solvents (e.g., DMSO, DMF, THF, etc.), however, the relative rates are completely reversed ... 

As emphasized in Section 1.2, however, the relative nucleophilicities of the halides is a somewhat tricky issue, and in polar, aprotic solvents the order of nucleophilicities is actually the reverse of the above. 

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