Nucleophilic aromatic high-pressure

H. Aromatic Nucleophilic Substitution with Amines under High Pressure... 

The electron spin resonance spectra were run in nitrogen-saturated solutions of aromatic compound ca. 10" m) and nucleophile (0-05-0-1 M) in the solvent(s) indicated. Irradiation in the cavity was effected with a high pressure mercury arc. Electrolysis was performed with the platinum cathode in the cavity, tetraethyl-ammonium perchlorate as electrolyte and electric currents of 10-250 /lA. 

Kotsuki [128] reported a straightforward approach to the synthesis of chiral 4-PPY (35, Fig. 7) catalysts via high-pressure promoted nucleophilic aromatic... 

Nucleophilic displacement of aryl halides is a useful route for the introduction of amino functionality into aromatic systems that are susceptible to nucleophilic attack186,187. The reaction may be catalyzed by copper and yields are particularly improved by the use of phase-transfer conditions188,189 or under high pressures of 5-10 kbar190-193. 

The concept of electron-rich P(f catalysts is based on the analogy between nucleophilic aromatic substitution (eq. (12a)) and Pd° insertion (cf. eq. (12b)) [42 c, d]. It had previously been applied in the carbonylation of aryl chlorides [38 a, b]. Related work by Milstein [42] and Basset [43] should be consulted. High-pressure conditions seem to enhance the aryl chloride reactivity, too [44]. Meanwhile, various other methods have been developed for the selective activation of aryl chlorides with defined Pd complexes as well as in situ systems (cf. Section 3.1.6.4). 

As expected from the depicted mechanism, early attempts to control the stereoselectivity of the MBH reaction was focused on the application of chiral amines (Fig. 4.48). Thus, using high pressure conditions (5 kbar) to accelerate the reaction and a C -symmetric DABCO derivative 245 (15 mol%), product 241a (R =Me, R sq-NO CgH ), was obtained in 45% yield and 47% ee (1 mol% hydroquinone, THF, 30°C) [318]. When used with pyrrolizidine derivative 246 (10 mol%, acetonitrile, 0°C) improved results (17-93% yield, 39-72% ee) were obtained in reactions between methyl or ethyl vinyl ketone (237a R =Me and 237b R =Et) and aromatic aldehydes. The presence of NaBF as co-catalyst was required to achieve these results, due to the coordination of aldehyde and hydroxy group of the catalyst to the alkali metal, which fixed the orientation for the attack of the nucleophile to the electrophile in the transition state [319]. 

A series of nucleophilic aromatic substitutions was systematically investigated by Verboom and coworkers in a high-pressure capillary microreactor [46]. p-Halonitrobenzenes (with X=F, Cl, Br) were reacted with a 10-fold excess of three different amines (pyrrolidine, piperidine and morpholine) at pressures up to 600 bar to give the corresponding p-N,N-dialkylaminonitrobenzenes (Scheme 4.23). The pressure dependences of the reaction rates were quantitatively analyzed with on-line... 

Aniline reacts with nitrous acid to give benzenediazonium salts, which react with a variety of reagents via a substitution reaction. These reagents include cuprous salts, aqueous acid, iodide, hypophosphorous acid, and activated benzene derivatives. Nucleophilic substitution at the sp carbon of a halo-benzene derivative does not occur unless high heat and pressure are used. Electron-withdrawing substituents on the benzene ring significantly lower the temperature required for the reaction. Nucleophiles for this nucleophilic aromatic substitution reaction include water, hydroxide, alkoxide, and amines. 

Verboom and coworkers developed a high-pressure microreactor setup that could investigate the influence of pressure on the aromatic nucleophilic substitution reaction of p-halonitrobenzenes with cyclic amines up to 600bar [25], The reaction... 

In Chapter 43 we also gave the structure of timolol, a thia diazole-based [3-blocker drug for reduction of high blood pressure. This compound has an aromatic 1,2,5-thiadiazole ring system and a saturated morpholine as well as an aliphatic side chain. Its synthesis relies on ring formation by rather a curious method followed by selective nucleophilic substitution, rather in the style of the last synthesis. The aromatic ring is made by the action of S2CI2 on cyanamide . 

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