SnAt reaction

Sjwyer and coworkers have developed an efficient alternative UUmann synthesis of diaryl ethers, diaryl thioethers, and diarylamines using the SnAt reaction. Phenol, thiophenol, or aniline reacts v/ith an appropriate aryl halide, In the presence of KF-aliunina and 18-crovm-6 In acetonitrile or DMSO to give the corresponding diaryl ether or diaryl thio ether as shovm In Eqs. 9.6 and 9.7. ... 

The SnAt reactions were first successfully used in the synthesis of high-molecular-weight poly(arylene etherjs by Johnson et al.4,5 This reaction represents a good example for poly(ether sulfonejs in general, either in laboratory -or industrial-scale preparations. In this procedure, the bisphenol A and sodium hydroxide with an exact mole ratio of 1 2 were dissolved into dimethyl sulfoxide (DMSO)-chlorobenzene. The bisphenol A was converted into disodium bisphenolate A, and water was removed by azeotropic distillation. After the formation of the anhydrous disodium bisphenolate A, an equal molar amount of 4,4,-dichlorodiphenyl sulfone (DCDPS) was added in chlorobenzene under anhydrous conditions and the temperature was increased to 160°C for over 1 h... 

Although the synthesis of multiple-pyrrolyl compounds can be achieved by SnAt reactions of perfluoroaromatics with pyrrolylsodium at ambient temperature <96JOC9012>, deleterious side reactions are often observed during attempted A-alkylations of the alkali salts of pyrrole. A protocol has therefore been developed for the preparation of N-arylmethylenepyrroles by reduction of the corresponding AT-acyl derivatives by treatment with sodium borohydride/boron trifluoride etherate in a sealed tube <96S457>. ... 

Pyrazines undergo nearly all of the same reactions as pyrimidines, from nucleophilic substitution (SnAt) to palladium-catalyzed cross coupling reactions. Displacement of the chlorides via SnAt reactions with nitrogen (157 158) and sulfur-based nucleophiles (158... 

After reviewing the literature, the scientist set out on optimization of the first key step, a SnAt reaction. Typical SnAt reaction conditions were initially attempted, examples of which can be seen in Table 8.4. Typical reflux heating in solvents such as DMF and DMSO provided poor yields of the desired products even after prolonged heating. Only with the use of a pressurized vessel were the satisfactory levels of the desired product obtained. However, it should be pointed out that under typical library production conditions, sealed tubes could not be used to produce the desired compounds, and in all actuality the use of refluxing DMSO would also be problematic. After examining... 

Makino et al.35 developed a solid-phase synthesis of 1,3-disubstituted 2-thioxoquinazoline-4-ones using HMP Lanterns that were derivatized with a 4-aminobenzoate ester. Following the assembly of amide 25 (Scheme 9), SnAt reaction with alkyl amines gave support-bound products 26 with high conversion. The key thiocarbonylation step was achieved with thiocarbo-nyldiimidazole in decalin at 95° for 16 h in the presence of DMAP to afford 1,3-disubstituted 2-thioxoquinazoline-4-ones 27. The target compounds 28... 

Scheme 41 High-pressure amino SnAt reaction of 2-chlorobenzimidazole (149) [94]...

The synthesis of FQ (Fig. 20) is simple and quite economical, which renders FQ attractive for the development of an antimalarial drug intended for use in areas, concerned by malaria, that are mostly overlaying with low-income countries. FQ was obtained starting from the commercially available AQV-dimethyl-1-ferrocenylmethanamine. The ferrocenic aldehyde results from a C-C bond formation, a two-step sequence involving metallation with tert/o-butyllithium and a reaction with DMF. This step has been previously studied and the 1,2 orientation of the two substituents of the cyclopentadienyl has been unambiguously established [125], The aldehyde is converted to the corresponding oxime, which is then reduced to the primary amine. The SNat reaction between the amine and 4,7-dichloroquinoline leads to the desired FQ [121]. 

The use of DMSO as a mechanistic tool is not restricted to rate variation effects (Section 4). Advantage can also be taken of its unique molecular properties which enable it to stabilize certain types of structures, such as the anionic intermediates in SnAt reactions. Moreover, as a consequence of its influence on ion association constants, it is found to affect the product distribution and the stereochemical course of bimolecular olefin-forming eliminations. These two illustrative systems which have been chosen for discussion are intended to demonstrate the versality of this solvent in mechanistic studies and may suggest other avenues of investigation. 

The simplest example of an aromatic nucleophilic substitution is the SnAt reaction between l-chloro-2,4-dinitrobenzene and piperidine, the two-step mechanism of which, given in Eq. (5-26), is now fully established [501-503], It involves formation of a Meisenheimer-type zwitterionic intermediate via a dipolar activated complex, followed... 

Su et al. [35] gave the mercury (ll)-catalyzed liquid phase synthesis of 1,2-disubstituted benzimidazoles (xxviii) by utilizing SnAt reactions, reduction and cyclization reaction. Tbe yield of the product ranged between 73-90%. 

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