Protic solvents also

Interestingly, the same authors [13b] have isolated the l,2-dihydro-l,2,4,5-tetra-zine intermediate 21 by condensation of 2-cyanopyridine 20 with hydrazine hydrate in presence of flower of sulfur (Scheme 8.9 b). The reaction time is reduced under the action of microwave irradiation (125 W) protic solvents also promote the transformation. 

Polar protic solvents also possess a pronounced ability to separate ion pairs but are less favorable as solvents for enolate alkylation reactions because they coordinate to both the metal cation and the enolate ion. Solvation of the enolate anion occurs through hydrogen bonding. The solvated enolate is relatively less reactive because the hydrogen-bonded enolate must be disrupted during alkylation. Enolates generated in polar protic solvents such as water, alcohols, or ammonia are therefore less reactive than the same enolate in a polar aprotic solvent such as DMSO. 

The luminescence properties of ligand 68 and its complexes have been examined.125 As shown in Figure 7, uncomplexed 68 exhibits a very weak luminescence band (d> < 5 X 10-5, t < 0.5 ns) centered at 540 nm in MeOH/H20 (1 1 v v), which is consistent with the luminescence behavior of 8-hydroxyquinoline in protic solvents. Also, no appreciable luminescence intensity increase was observed from pH 2 to 13 with uncomplexed 68. However, addition of Mg2+ to 68 (5 x 10 5 M) in a neutral (1 1 v v) MeOH/H20 solution (pH 7.2) results in a strong enhancement of the luminescence band ( = 0.042, t = 7.4 ns). Upon complexation with Mg2+ and excitation at 393 nm, the fluorescence intensity of 68 is increased by a factor of 1000. The excitation spectrum of the complex strictly matches the absorption spectrum of 68-Mg2+, suggesting that the observed fluorescence is due to neutral complex formation. 

This ozonolysis method has also been applied to 0-methyl ketone oximes 204, in the absence of carbonyl compounds or protic solvents, also affording tetroxanes (Scheme 36). The method has been extended to the synthesis of dispirotetroxanes devoid of the usual hexaoxonane by-products often seen in acidic peroxidation reactions (see Section 9.14.8.3) <2002RMC113>. 

In fee absence of fee solvation typical of protic solvents, fee relative nucleophilicity of anions changes. Hard nucleophiles increase in reactivity more than do soft nucleophiles. As a result, fee relative reactivity order changes. In methanol, for example, fee relative reactivity order is N3 > 1 > CN > Br > CP, whereas in DMSO fee order becomes CN > N3 > CP > Br > P. In mefeanol, fee reactivity order is dominated by solvent effects, and fee more weakly solvated N3 and P ions are fee most reactive nucleophiles. The iodide ion is large and very polarizable. The anionic charge on fee azide ion is dispersed by delocalization. When fee effect of solvation is diminished in DMSO, other factors become more important. These include fee strength of fee bond being formed, which would account for fee reversed order of fee halides in fee two series. There is also evidence fiiat S( 2 transition states are better solvated in protic dipolar solvents than in protic solvents. 

For the other broad category of reaction conditions, the reaction proceeds under conditions of thermodynamic control. This can result from several factors. Aldol condensations can be effected for many compounds using less than a stoichiometric amount of base. Under these conditions, the aldol reaction is reversible, and the product ratio will be determined by the relative stability of the various possible products. Conditions of thermodynamic control also permit equilibration among all the enolates of the nucleophile. The conditions that permit equilibration include higher reaction temperatures, protic solvents, and the use of less tightly coordinating cations. 

Aromatic denitrocyclizations have been used for many years in some well-known synthetic reactions. Probably the best known example is the Turpin synthesis of phenoxazines and similar synthesis of phenothiazines. The classical setup used usually base-catalyzed reactions in polar protic solvents, very often alcohols. In many cases using polar aprotic solvents was found advantageous. Besides the mentioned influence of the H-bonding, better ionization and lower solvation of the nucleophile are also important. Sf Ar reactions proceed through strongly polarized complexes, which are well soluble and highly polarized in polar aprotic solvents. 

El eliminations begin with the same uni molecular dissociation we saw in the Sfsjl reaction, but the dissociation is followed by loss of H+ from the adjacent carbon rather than by substitution. In fact, the El and SN1 reactions normally occur together whenever an alkyl halide is treated in a protic solvent with a non-basic nucleophile. Thus, the best El substrates are also the best SN1 substrates, and mixtures of substitution and elimination products are usually obtained. For example, when 2-chloro-2-methylpropane is warmed to 65 °C in 80% aqueous ethanol, a 64 36 mixture of 2-methyl-2-propanol (Sjql) and 2-methylpropene (El) results. 

OS 38] [reactor and protocol given in [107]] By reaction of N,N-dimethylaniline with 4-nitrobenzenediazonium tetrafluoroborate, the corresponding azobenzene derivative is obtained at a conversion of 37% using methanol (protic solvent) or acetonitrile (aprotic solvent) under electroosmotic flow conditions [107] (see also [14]). 

In the following, we write the protic solvents conventionally as SH, where H is the proton and S is the solvent residue. They include many compounds with -OH and >NH groups, also some others (Table 8.1). All these solvents are polar, have... 

Allyl p-tolyl sulphoxide 535 reacts with sodium methoxide in methanol by initial prototropic isomerization and subsequent addition of methanol to give 536 (equation 333). Protic solvents are photochemically incorporated by the open chain olefinic bond of trans methyl )S-styryl sulphoxide 537 in a Markovnikov regiospecificity (equation 334). Mercaptanes and thiophenols add to vinyl sulphoxides in a similar manner (compare also Reference 604 and Section IV.B.3) to give fi-alkylthio(arylthio)ethyl sulphoxides 538 (equation 335). Addition of deuteriated thio-phenol (PhSD) to optically active p-tolyl vinyl sulphoxide is accompanied by a low asymmetric a-induction not exceeding 10% (equation 336) . Addition of amines to vinyl sulphoxides proceeds in the same way giving )S-aminoethyl sulphoxides in good to quantitative yields depending on the substituents at the vinyl moiety When optically active p-tolyl vinyl sulphoxides are used in this reaction, diastereoisomeric mixtures are always formed and asymmetric induction at the p- and a-carbon atoms is 80 20 (R = H, R = Me) and 1.8 1 (R = Me, R = H), respectively (equation 337) ... 

The solvent can also affect regioselectivity. Consider O- vs C-alkylation of phenoxide ion with allyl chloride or bromide. In water, with allyl chloride the O- to C-alkylation ratio is 49 41 with phenol as a solvent it is 22 78 with methanol, dimethylformamide, and dioxane 100% O-alkylation is achieved. The selective solvation of the more electronegative O by the more protic solvents perhaps leads to some C-alkylations. 

Tri-n-butyltin hydride can also be used for reductive demercuration.20 An alternative reagent for demercuration is sodium amalgam in a protic solvent. Here the evidence is that free radicals are not involved and the mercury is replaced with retention of configuration.21... 

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