A pragmatic procedure for predicting regioselectivity in nucleophilic substitution of aromatic fluorides

The scope and limitations of a method for predicting the regioisomer distribution in kinetically controlled nucleophilic substitution reactions of aromatic fluorides have been investigated. This method is based on calculating the relative stabilities of the isomeric σ-complex intermediates using DFT. A wide set of substrates and anionic nucleophiles have been investigated. Predictions from this method can be used quantitatively—these agree to an average accuracy of ±0.5 kcal/mol with experimental observations in eleven of the twelve investigated reactions.     

Solvent-controlled leaving-group selectivity in aromatic nucleophilic substitution

A solvent-controlled inversion of leaving group ability allows selective access to either of two internal substitution products in S(N)Ar reactions of substrates with competing leaving groups. Application of this principle in a selective synthesis of the highly functionalized xanthone core of the antibiotic FD-594 is presented.     

Iron-assisted nucleophilic aromatic substitution on solid phase

Iron-assisted S(N)Ar reactions were performed for the first time on solid phase, and a library of 36 unsymmetrically substituted phenylpiperazines and phenyl-1,4-diazepanes was synthesized with this novel strategy. The scope of iron-assisted S(N)Ar reactions on solid phase was investigated, and reactions of representative nucleophiles from groups VI (O, S, and Se) and V (N and P) of the periodic table were examined. Decomplexation of resin-bound iron complexes was achieved with 1,10-phenanthroline under irradiation, thereby overcoming the notorious disadvantages of decomplexation observed in solution-phase chemistry.     

Unusual dealkylations and rearrangements in aromatic nucleophilic substitution

The reaction of 2,4-dinitrohalobenzenes with di-isopropylamine produces mainly N-(2,4-dinitrophenyl)-isopropylamine and N-(2,4-dinitrophenyl)-n-propylamine instead of the expected straightforward substitution product. Dealkylations are also observed in the reactions with isopropylcyclohexylamine and dicyclohexylamine. A carbanionic mechanism is proposed.     

Novel gas-phase ion-molecule aromatic nucleophilic substitution in beta-carbolines

We report a novel gas-phase ion-molecule aromatic-nucleophilic substitution reaction between beta-carbolines and water vapour, that accounts for the observation of ions with higher masses than the precursor ion in the MS/MS spectra.     

Imidazole as leaving group in aromatic nucleophilic substitution reactions

The reaction of N-(2,4,6-trinitrophenyl) imidazole with n-butylamine is pH dependent. A mechanism involving acid catalyzed leaving group departure is suggested.     

First nucleophilic aromatic substitution of annelated pyrazole.

3-Chloropyrazolo[3,4-c]quinoline 5, 3-chloropyrazolo[3,4-c]isoquinoline 6, 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]quinolin-3-one 8, and 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]isoquinolin-3-one 10 were obtained by acid-induced nucleophilic aromatic substitution (S(N)H) of H-3 in N-hydroxypyrazolo[3,4-c]quinoline 1b and in N-hydroxy pyrazolo[3,4-c]isoquinoline 3b. In the acid-induced chlorination, 3b was far more reactive than 1b, whereas the related N-hydroxypyrazolo[4,3-c]quinoline 2b and N-hydroxypyrazolo[4,3-c]isoquinoline 4b were completely unreactive toward S(N)H under identical conditions.     

Thianthrene-containing polyimides with monomer formation via nucleophilic aromatic substitution

Thianthrene-2,3,7,8-tetracarboxylic dianhydride was synthesized via nucleophilic aromatic substitution of N-phenyle-4,5-dichlorophthalimide with thiobenzamide, thioacetamide, and sodium sulfide. This monomer was then polymerized with aromatic diamines by the con-ventional low temperature technique in N,N-dimethylacetamide (DMAc) to yield soluble poly(amic acid)s. Polyimides were obtained by thermal cyclization of the poly(amic acid) films. Polymers obtained formed creasable thin films and had excellent thermal stability in air and nitrogen. The bent thianthrene structure limited crystallization and chain packing, as indicated by x-ray analysis. The amorphous thianthrene-containing polyimides were only soluble in H₂SO₄. © 1995 John Wiley & Sons, Inc.     

Intramolecular aromatic nucleophilic substitution of the benzimidazole-activated nitro group

A wide range of 2-(2-nitrophenyl)-1H-benzimidazoles undergo high-yielding intramolecular S(N)Ar of nitrite with N-pendant alkoxides under mild conditions (DMF, rt). When this operationally simple process is carried out at elevated temperatures in the presence of excess NaH, the initially formed S(N)Ar products are converted to the corresponding N-vinyl-substituted 2-(2-hydroxyphenyl)-1H-benzimidazoles via base-catalyzed isomerization. [reaction: see text]     

Efficient nucleophilic aromatic substitution between aryl nitrofluorides and alkynes

The nucleophilic aromatic substitution reaction between electron-deficient aryl fluorides and terminal alkynes is shown to be efficiently promoted by sodium bis(trimethylsilyl)amide as a base. Moderate to excellent yields of 2-ethynylnitrobenzene products can be obtained under mild conditions.     

New highly stable metallabenzenes via nucleophilic aromatic substitution reaction

Treatment of the ruthenabenzene [Ru{CHC(PPh(3))CHC(PPh(3))CH}Cl(2)(PPh(3))(2)]Cl (1) with excess 8-hydroxyquinoline in the presence of CH(3)COONa under air atmosphere produced the S(N)Ar product [(C(9) H(6)NO)Ru{CHC(PPh(3))CHC(PPh(3))C}(C(9)H(6)NO)(PPh(3))]Cl(2) (3). Ruthenabenzene 3 could be stable in the solution of weak alkali or weak acid. However, reaction of 3 with NaOH afforded a 7:1 mixture of ruthenabenzenes [(C(9)H(6)NO)Ru{CHC(PPh(3))CHCHC}(C(9)H(6)NO)(PPh(3))]Cl (4) and [(C(9)H(6)NO)Ru{CHCHCHC(PPh(3))C}(C(9)H(6)NO)(PPh(3))]Cl (5), presumably involving a P-C bond cleavage of the metallacycle. Complex 3 was also reactive to HCl, which results in a transformation of 3 to ruthenabenzene [Ru{CHC(PPh(3))CHC(PPh(3))C}Cl(2)(C(9)H(6)NO)(PPh(3))]Cl (6) in high yield. Thermal stability tests showed that ruthenabenzenes 4, 5, and 6 have remarkable thermal stability both in solid state and in solution under air atmosphere. Ruthenabenzenes 4 and 5 were found to be fluorescent in common solvents and have spectral behaviors comparable to those organic multicyclic compounds containing large π-extended systems.