N-substituted Indoles Research Articles

First example of regiospecific intermolecular C-H insertion reactions of cyclic rhodium carbenoids: novel synthesis of 3-indol-3'-yloxindoles.

Facile regiospecific intermolecular C-H insertion reactions of cyclic rhodium carbenoids have been achieved using diazo carbonyl compounds 1 and indole or N-substituted indoles to afford 1,3-dihydro-1'H-[3,3']biindolyl-2-ones, 3a-o in an excellent yield.

Indoles as Nucleophiles in a Self-Catalytic Michael Reaction

C-3 Substituted indoles 7a-c were regioselectively synthesized in high yields by reacting indole 2 and electron-rich indoles 3,4 with acrylate 1. Additions of electron-deficient indoles 5.6 to the acrylate 1 gave N-substituted indoles 9a,b.

Synthesis of 2,3-dihydroindoles, indoles, and anilines by transition metal-free amination of aryl chlorides.

Aliphatic and aromatic amines react with 2- and 3-chlorostyrene in the presence of potassium tert-butoxide to give N-substituted 2,3-dihydroindoles in good yields. The combination of this domino-amination protocol with a suitable dehydrogenation reaction gives access to pharmacologically interesting indoles in a one-pot procedure. Overall product yields of N-substituted indoles >50% are obtained by this method starting from commercially available substrates. In addition to the intramolecular base-promoted amination of aromatic C-Cl bonds, metal-free intermolecular aminations of aryl chlorides with primary and secondary amines are described. The use of potassium tert-butoxide as base allows the synthesis of various anilines in good to excellent yields. Due to the formation of aryne intermediates, either N-substituted anilines or meta-substituted anilines are produced with excellent selectivities.

Formation of stable vesicles from N- or 3-alkylindoles: possible evidence for tryptophan as a membrane anchor in proteins.

Twelve indole derivatives have been prepared and studied. Five were 1-substituted: 1, methyl; 2, n-hexyl; 3, n-octyl; 4, n-octadecyl; and 5, cholestanyloxycarbonylmethyl. Four were 3-substituted: 6, methyl; 7, n-hexyl; 8, n-octyl; and 9, n-octadecyl. Three were disubstituted as follows: 10, 1-n-decyl-3- n-decyl; 11, 1-methyl-3-n-decyl; and 12, 1,3-bis(n-octadecyl)indole. Sonication of aqueous suspensions afforded stable aggregates from 3-5 and 8-12. Laser light scattering, dye entrapment, and electron microscopy were used to characterize the aggregates. Aggregates formed from N-substituted indoles proved to be more robust than those formed from 3-alkylindoles. A stable monolayer formed from 3-n-octadecylindole but not from N- or 1,3-disubstituted analogues by using a Langmuir-Blodgett trough. The formation of aggregates was explained in terms of stacking by the relatively polar indole headgroup. In the monolayer experiment, this force was apparently overwhelmed by H-bonding interactions with the aqueous phase.

Organotin mediated nitration in heteroaromatic series using tetranitromethane or dinitrogen tetroxide

2-Trimethylstannylated benzo[ b]furan, benzo[ b]thiophene, N-substituted indoles and pyridine afford the corresponding nitro derivatives in regioselective fashion upon treatment with tetranitromethane (using sun-lamp irradiation in the case of N-containing heterocycles) or with dinitrogen tetroxide.

Convenient preparation of N-substituted indoles by modified Leimgruber-Batcho indole synthesis

A modified reductive alkylation of pre-indole 3, prepared from readily available Leimgruber-Batcho indole synthesis derived intermediates, followed by acidic methanolysis generates 6-carbomethoxy-N-substituted indoles. The three step preparation of pre-indole 3 from substituted 2-nitrotoluene 1 in 66% yield and conversion to a variety of N-substituted indoles is presented.

Lithiation Routes to Oxidoles and 2-indolinethiones: Precursors to 2,2'-Dithiobisindoles with Tyrosine Kinase Inhibitory Properties

N-Substituted oxindoles and 2-indolinethiones can be prepared by lithiation of carboxyl protected N,2-dimethylanilines followed by quenching with CO 2 or CS 2 respectively. 2-Indolinethione derivatives are also available via demethylation of 2-methylthioindoles, which are prepared by lithiation of N-substituted indoles and treatment with dimethyl disulfide

Simulation of 13C nuclear magnetic resonance spectra of indoles

Linear models are developed to predict the 13C NMR chemical shifts of carbons in indole moieties based on a critical review. These models fill a gap in the spectral simulation database which is used to simulate the 13C NMR spectra of a wide range of organic compounds, illustrating that this is a viable method for the expansion of the database. The models are based on calculated numerical parameters (descriptors) which encode the topological and topological-electronic environments of the eight indole carbons. The 56 indoles in the reference set have a mean r.m.s. error of 0.93 ppm and the 42 indoles in the prediction set have an error of 2.04 ppm. The spectral error for N-substituted indoles is higher than that of N-unsubstituted indoles.

Removable Groups for Activation of Indole Photochemistry

The ability of a series of nitrogen-substituents to activate the cycloaddition photochemistry of indoles has been examined; the N-substituents were chosen in order to enable their removal following cycloaddition under mild neutral, acidic or basic conditions. N-Substituted indoles, 1 a-g, were prepared in which the N-substituent is COPh, CO 2 Et, CO 2 CH 2 CH 2 SiMe 3 , CO 2 CH 2 CH 2 CN, CO 2 Bu-t, CO 2 Ph, and CO 2 CH 2 Ph, respectively

Regio- and Chemoselective Alkylation of 2,3-Dialkylindoles. A Convenient Preparation of 2,3,3-Trialkyl-3H-indoles

Various 3-alkyl-2,3-dimethyl-3H-indoles were prepared by addition of an alkyl iodide to a solution of the lithium salt of 2,3-dimethylindole. In contrast, reaction with ethyl chloroformate or trimethylsilyl chloride afforded the N-substituted indoles exclusively. The reaction failed with cyclohexylcarboxaldehyde

Synthetic Applications of Reactions of N-Substituted Pyrroles and Indoles with Palladium Acetate

Synthetic Applications of Reactions of N-Substituted Pyrroles and Indoles with Palladium Acetate

Synthesis of N-substituted indoles by extractive alkylation

A method was developed for the N-alkylation of indole and its derivatives by alkyl halides in the presence of sodium hydroxide and catalytic amounts of trimethylbenzylammonium chloride.

The reactions of acetylenic esters with N-substituted indoles

Reaction of an arylpropiolic ester with indol-1-ylacetamide and ethyl indol-1-ylacetate in the presence of sodium ethoxide yielded 4-aryl-3-(indol-1-yl)pyridine-2,6(1H,3H)-diones and ethyl arylpropioloyl- (indol-1-yl)acetates respectively. Reaction of arylpropiolic esters with 1-acetylindole in the presence of sodium ethoxide at 0� yielded two products, 5-aryl-1-(indol-1-yl)pent-4-yne-1,3-dione and ethyl 8-(indol-1-yl)cinnamates, as a result of Claisen and Michael reactions respectively. These products were identified on the basis of spectral and analytical data.

The synthesis of isoquinolines, indoles and benzthiophen by an improved Pomeranz-Fritsch reaction, using boron trifluoride in trifluoroacetic anhydride

Pomeranz-Fritsch cyclisations are reported using a new reagent boron trifluoride-trifluoroacetic anhydride. Isoquinolines carrying 7-OMe groups have been prepared in good yields and the method extended to the formation of N-substituted indoles and of benzthiophen from the corresponding acetals. Benzofuran could not be obtained by this procedure nor could a Bischler-Napieralski type cyclisation be induced. In the latter case the aromatic ring of the starting amide was acetylated when suitably activated.

Aminoalkylation of metal derivatives of indole. Part III. Alkylation of lithio-derivatives of N-substituted indoles with 1-chloro-2-dimethylaminoethane

1-Methyl- and 1-phenyl-indolyl-lithium, when treated with 1-chloro-2-dimethylaminoethane, underwent aminoalkylation at the 2-position of the indole nucleus whereas the lithio-derivatives of 1-benzyl- and 1-benzyl-3-phenylindole yielded products derived by substitution at the α-position of the benzyl group. The structures of the amines were confirmed by 1H n.m.r. spectra and by hydrogenolysis experiments. The syntheses of 1-phenyl- and 1-benzyl-3-phenyl-indoles are described.