Nucleophilic aromatic substitution (SNAr)
9 real reactions from the literature, on aryl fluorides, aryl chlorides, aryl bromides and heteroaryl fluorides. Each scheme shows starting materials, conditions and products, with the yield and reference where the source reports them.
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SNAr: 4-bromo-5-nitroveratrole (an aryl bromide) with MeSH; K2CO3 gives (4,5-dimethoxy-2-nitrophenyl)(methyl)sulfane (the substituted arene). 79% yield.
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SNAr: diethyl methylmalonate (a malonate ester) and 2,4-dichloro-5-fluoropyrimidine (a heteroaryl fluoride) with NaH gives the substituted arene. 98% yield.
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SNAr: cyclohexylhydrazine (a primary amine) and 2',4'-difluoropropiophenone (an aryl fluoride) with NaOAc (weak base) gives 1-cyclohexyl-3-ethyl-6-fluoro-1H-indazole (the substituted arene). 98% yield.
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SNAr: 2-fluoro-5-nitro-2'-(trifluoromethoxy)-1,1'-biphenyl (an aryl fluoride) with MeONa gives the substituted arene. 93% yield.
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SNAr: 4-fluorobenzaldehyde (an aryl fluoride) and 4-methoxyphenol with K2CO3 gives 4-(4-methoxyphenoxy)benzaldehyde (the substituted arene). 89% yield.
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SNAr: 4,4'-bipyridine and 1-chloro-2,4-dinitrobenzene (an aryl chloride) with hint: product is a salt gives 1-(2,4-dinitrophenyl)-4-pyridin-4-ylpyridin-1-ium (the substituted arene).
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SNAr: homoveratrylamine (a primary amine) and 1-fluoro-2-nitrobenzene (an aryl fluoride) with iPr2NEt gives N-[2-(3,4-dimethoxyphenyl)ethyl]-2-nitroaniline (the substituted arene). 100% yield.
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SNAr: 2,3,4-trifluorobenzoic acid (an aryl fluoride) and 2-chloro-4-iodoaniline (an aryl iodide) with excess; LiNH2 gives 2-(2-chloro-4-iodoanilino)-3,4-difluorobenzoic acid (the substituted arene). 50% yield.
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SNAr: 2,4-dichloronitrobenzene (an aryl chloride) with Na2S gives the substituted arene. 50% yield.