Nucleophiles salts

Solid-liquid PTC conditions in which the nucleophilic salts (organic or mineral) are transferred from the solid state (as they are insoluble) to the organic phase by means of a phase-transfer agent. Most often the organic nucleophilic species can be formed by reaction of their conjugated acids with solid bases (sodium or potassium hydroxides, or potassium carbonate) (Scheme 5.1 path b). Another proposed mechanism suggests that interfacial reactions occur as a result of absorption of the liquid phase on the surface of the solid. 

It is important to differentiate between the effects of a nonnucleophilic salt such as Mg(C104)2 on one hand, and a weak nucleophilic salt such as Et4NOAc on the other. The effect of nonnucleophilic salts on photo-oxygenation via electron transfer can be understood as the stabilization of ion-radicals by coulombic interaction, resulting in the suppression of a back electron transfer between ion-radicals. The weak nucleophilic salts cause unusual effects. The addition of the anionic nucleophile to the cation-radical and complexation of the weak nucleophilic salt with the ion-radicals bring about these effects. 

There are at present three general types of qualitative tests for the epoxido function. The first depends on the fact that treatment- f an epoxjde with concentrated aqueous solutions of nucleophilic salts releases OH ions into solution. The second is baaed oti hydration aiul oxidative cleavage of the resulting 1,2-diol with a suitable reagcrii. The last depends on the ability of various tertiary aromatic bases like pyridine to form intensely -colored complexes with epoxides. TIr-m-three approaches will now be considered in turn. 

A comparison of the suitability of solvents for use in Srn 1 reactions was made in benzenoid systems46 and in heteroaromatic systems.47 The marked dependence of solvent effect on the nature of the aromatic substrate, the nucleophile, its counterion and the temperature at which the reaction is carried out, however, often make comparisons difficult. Bunnett and coworkers46 chose to study the reaction of iodoben-zene with potassium diethyl phosphite, sodium benzenethiolate, the potassium enolate of acetone, and lithium r-butylamide. From extensive data based on the reactions with K+ (EtO)2PO (an extremely reactive nucleophile in Srn 1 reactions and a relatively weak base) the solvents of choice (based on yields of diethyl phenylphosphonate, given in parentheses) were found to be liquid ammonia (96%), acetonitrile (94%), r-butyl alcohol (74%), DMSO (68%), DMF (63%), DME (56%) and DMA (53%). The powerful dipolar aprotic solvents HMPA (4%), sulfolane (20%) and NMP (10%) were found not to be suitable. A similar but more discriminating trend was found in reactions of iodobenzene with the other nucleophilic salts listed above.46 Nearly comparable suitability of liquid ammonia and DMSO have been found with other substrate/nucleophile combinations. For example, the reaction of p-iodotoluene with Ph2P (equation (14) gives 89% and 78% isolated yields (of the corresponding phosphine oxide) in liquid ammonia and DMSO respectively.4 ... 

When sodium hydroxide was used as nucleophile, salt 3c was rapidly converted to alkyne 63. This alkyne now features only a single stereocenter, and this is evident from its spectra. Its structure was initially assigned incorrectly, but the alkyne structure (63) has been rigorously established by X-ray crystallography. It is curious that azide and hydroxide should attack on the periphery of the TTF ring system, while the bulkier malonate anion attacks internal carbons. It is also intriguing that none of the observed modes of attack give rise to the sulfur ylid 64, which should be more stable than 61. 

Sufficiently rapid exchange among species of different reactivities and different lifetimes thus, the rate of deactivation (return to the dormant species from the cationic counterpart) should be comparable with that of propagation. This can be accomplished by using weak Lewis acids, nucleophiles, salts, as well as nonpolar media. 

This allows the in situ preformation of nucleophilic salts followed by anionic reaction (PTC), both steps being favoured independently by microwaves (Scheme 23). 

The formaldiminium ion formed from the reaction of 4-hexynylamine (90 R = R = Me) with paraformaldehyde and camphorsulfonic acid is reported not to cyclize when heated for 1 h at 1(X) C in the weakly nucleophilic solvent acetonitrile. However, when nucleophilic salts are added the 3-alkylidene-piperidines (91) are formed in good yields (Scheme 32). Attempted cyclizations of (90) in the presence of weaker nucleophiles such as benzenethiol or methanol were less effective, the former yielding <15% of the expected alkylidenepiperidine product, while the latter provided no products of cyclization. If the strong nucleophile iodide is employed, even a weakly nucleophilic terminal alkyne can be successfully cyclized. In all of these cyclizations of 4-alkynylamines only formation of a six-membered ring product was observed. The (2)-stereochemistry of the alkylidene side chain evolves from antarafacial addition of the internal iminium cation and the external nucleophile to the alkyne. 

Solid-Liquid PTC. Despite the many applications in organic synthesis of SLPTC, only a few studies have reported the mechanism and kinetics of the SLPTC cycle. In carrying out a substitution reaction in a solid-hquid system, the quat (Q X ) approaches the solid surface and undergoes ion exchange with the solid nucleophilic salt at or near the solid interface (or in some cases within the solid) to form Y, followed by reaction oiQ Y with the organic substrate RX. 

Equation 8.28 shows only the anionic nucleophile explicitly, since the counterion does not appear to take part in the reaction. Nevertheless, the counterion affects the solubility of a nucleophilic salt, which therefore can influence the polarity of the solvent needed for the reaction. An alternative to the use of a more polar solvent to dissolve a salt for nucleophilic substitution is to use crown ether additives. Crown ethers are cyclic polyethers that can coordinate with cations and therefore increase their solubility in organic solvents. The nomenclature provides the total number of atoms and the number of oxygen atoms in the ring. Compoimd 51 is 12-crown-4, and 52 is 18-crown-6 (Figure 8.32). Coordination of a crown ether with a cation helps to dissolve the salt in a less polar solvent and leaves the anion relatively unsolvated. The activation energy for substitution therefore does not include a large term for desolvation of the nucleophilic anion, and the reactions are fast. For example, adding dicyclohexano-18-crown-6 (53) to a solution of 1-bromobutane in dioxane was found to increase its reactivity with potassium phenoxide by a factor of 1.5 x 10. Moreover, Liotta and Harris were able to use KF solubilized with 18-crown-6 (52) to carry out Sn2 reactions on 1-bromooctane in benzene. ... 

In order to prepare the catalytic bed, the catalyst is dissolved in a low-boiling solvent (methylene chloride, methanol), the nucleophile salt (alkaline halide or carboxylate) or the inorganic base (NaHCO or porous inorganic solid (alumina or silica... 

Under GL-PTC conditions, the iodide ion reacts with the alkyl halide and is removed from the column as alkyl iodide (ethyl iodide in Fig. 2). Moreover, Figure 2 shows that this is a real phase-transfer process in fact if the only function of the catalyst were to supply a liquid phase to act as solvent for the nucleophile salt it would... 

LL-PTC) or less probably in the organic phase through the HCO or CO3 anion-transfer from the solid phase to the liquid catalyst as counterion. Equation 11 represents the catalyst regeneration and is required in order that the reaction may occur. Strictly comparable with the analogous equation for SL-PTC, it represents the real function of the catalyst that is able to promote the exchange between its anion and the nucleophile salt. 

When non-nucleophilic salts, for example, L1C104, are included in the reaction medium, products indicative of a more reactive intermediate with carbocationic character are observed ... 

Yamashita, T, Tsurusako, T, Nakamura, N., Yasuda, M., and Shima, K., Electron transfer photosensitized oxygenation of stilbene and naphthalene derivatives in the presence of acetate ion controlling the reaction of the cation radicals by weak-nucleophilic salts. Bull. Chem. Soc. Jpn., 66, 857, 1993. 

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