Indole-2-acetonitrile, synthesis

Reaction of l-Methylpyrrole-2-acetonitrile 43 with 6 New Efficient Synthesis of Highly Substituted Indoles (Type-IV, 4a Model)... 

Pd(Ph3P)4 and Et3N in refluxing acetonitrile to form the intramolecular Heck cyclization product 152 [125]. The mechanism is akin to that of the Mori-Ban indole synthesis (see page 24). In another case, the intramolecular Heck cyclization of enamidone 153 with a pendant thienylbromide moiety furnished the 6-trig-endo product, indolizine 154, in 63% yield, along with the debrominated enamidone 155 in 37% yield [126],... 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

A general and efficient synthesis of 5-oxygenated indoles 126 and 128 has been reported by Kita et al. (92H503). The method involves intramolecular imine formation from p-benzoquinones 125 and p-benzoquinone monoacetals 127 bearing the 2-aminoethyl side chain. Compounds 125 and 127 are prepared by the oxidation of 124 with IBTA in acetonitrile in the presence of water and methanol, respectively (Scheme 35). 

Addition of methyllithium to the lactone 1219, followed by reduction with sodium borohydride in refluxing ethanol, afforded, almost quantitatively, ellipticine (228). Reaction of the compound 1219 with the lithio derivative of formaldehyde diethylmercaptal, and reduction with sodium borohydride in refluxing ethanol, led to the mercaptal 1221. Cleavage of the mercaptal 1221 with bis(trifluoroacetoxy) iodobenzene [Phl(OCOCF3)2] in aqueous acetonitrile gave the 11-formyl derivative, which was reduced with sodium cyanoborohydride (NaBHsCN) to 12-hydroxyellipticine (232) (710,711) (Scheme 5.202). The same group also reported the synthesis of further pyiido[4,3-fc]carbazole derivatives by condensation of 2-substituted indoles with 3-acetylpyridine (712). 

Enantioselective additions of a,f)-unsaturated 2-acyl imidazoles, catalyzed by bis(oxazolinyl)pyridine-scandium(III)triflate complex, were used for the asymmetric synthesis of 3-substituted indoles. The complex 114 was one of the most promising catalysts. The choice of acetonitrile as the solvent and the use of 4 A molecular sieves were also found to be advantageous. The 2-acyl imidazole residue in the alkylation products of u,(i-unsaturated 2-acyl imidazoles could be transformed into synthetically useful amides, esters, carboxylic acid, ketones, and aldehydes (Scheme 32) [105]. Moreover, the catalyst 114 produced both the intramolecular indole alkylation and the 2-substituted indoles in good yield and enantioselectivity (Scheme 33) [106]. The complex... 

In the previous reaction when the solvent was changed to acetonitrile-methanol, quinone monoacetals were formed. Both products were used for the synthesis of 5-oxygenated indoles [11], This type of transformation also occurred using DIB (Section 3.3) however, the use of BTI activated 4-alkyl phenols which reacted not only with methanol but also with other nucleophiles, simple ones such as water and fluoride, or more complex, according to the general scheme ... 

Synthesis of radioactively labelled indole-3-acetaldehyde, indole-3-ace-taldoxime and indole-3-acetonitrile... 

When intermediate 81 is formed from indole 80 and l,l -carbonyldiimidazole (GDI) using DMAP to promote indole nitrogen acylation in acetonitrile at reflux, it is reasonably stable, observed by TLC, but not isolated. Treatment of intermediate 81 in situ with amines, alcohols, or thiols afforded the desired derivatives 82. During the reaction of indoles with GDI, some carbonyl diindole 83 was formed. In many cases this material could be isolated and characterized. In an alternative approach, alcohols reacted with GDI stoichiometrically to form an unstable intermediate carbamate species 84, which could in turn be reacted with indoles to form the desired indole-1-carboxylates 82. This new methodology for the formation of compound 82 proved to be useful in one of the approaches for the synthesis of novel Serotonergics. 

The direct synthesis by anodic oxidation of a new series of electrically conducting poljnners is described.. Our polymers derive from sulfur and/or nitrogen containing hetero-cycles such as 2-(2-thienyl)pyrrole, thiazole, indole, and phthalazine. The anodic oxidation of these monomers is carried out in acetonitrile solutions containing tetrabu-tylammonium salts (TBA X ) ith X = BF, tetraethylammonium salt, TEA H C-C H -S0. Characterization of the materials by electrical conductivity, electron spin resonance, uv-visible spectroscopy, and cyclic voltammetry is discussed. 

For the synthesis of dibenzofuran (201), dibenzothiophenes (202), and carbazoles (203) by benzannelation, in the same manner, the 3-acetonitrile of benzo(b)furan, benzo(b)thiophen, and of indole are used ... 

An elegant photochemical formation of an aryl-carbon bond through a PET mechanism was recently reported in the total synthesis of the potent antimitotic polycycle (-)-diazonamide A. The reaction was initiated by intramolecular electron transfer between the indole chromophore and the adjacent bromoarene (Scheme 2.10). Thus, compound 21 was treated with an aqueous-acetonitrile solution of LiOH and the resulting lithium phenoxide solution was degassed and photolyzed (Rayonet, 300 nm) to yield biaryl 22 (as a single atropodiastereomer) in a good yield. A radical-radical anion pair (23) was formed upon excitation, and... 

Metal-catalysed cyclization is an increasingly important method of synthesis (reviews [B-4I, 2998, 3069, 3501, 3505 ). Bis(acetonitrile)dichloropalladium promotes cyclization of an alkynyl carbamate with epoxypropane and a vinyl chloride [3438] an alkynylaniline is converted into an indole by heating with a palladium chloride-triphenylphosphine catalyst [3631]. Mercury(II) acetate is an effective promotor of the cyclization of the alkenylaniline (37.2) to a reduced carbazole [3861]. 

The synthesis of Trp-P-2[2] started with an intermediate, indole-2-acetonitrile[9](24), prepared from commercially available indole-2-carboxylic acid[87. Vilsmeier reaction(25) of [9], with dimethylacetamideand phosphoryl chloride, gave 3-acetylindole-2-acetonitrile[10]. Cyclization of [10] on treatment with methanolic ammonia and aromatization involving a hydrogen transfer of the a-methylene group yielded the desired 3-amino-l-methyl-5H-pyrido (4,3b)indole[2] m/e 197(M+) vmax(KBr) 1635,1605 cm l 6 (CD3OD) 2.3(3H,s), 5.92(lH,s), 6.53-7.00(3H,m), 7.35(lH,d). 

Indole-2-acetonitrile[9] prepared from the Reissert compound (27). Ethyl 2-cyano-l,2dihydroquinoline-l-carboxylate[ll] was chosen as an intermediate for the synthesis of Trp-P-2. The photo-... 

Fukuyama s tin-mediated indole synthesis was also highlighted in the enantio-selective total synthesis of aspidophytine [45]. Treatment of the 2-alkenylphenyli-sonitrile 54 with tributyltin hydride and AIBN in refluxing acetonitrile followed by treatment of the 2-stannyl indole intermediate with iodine gave the expected 2-iodoindole 55, bearing methoxy groups at C-6 and C-7 of the indole ring, in 85% yield. 

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