Indoles 3-ethyl

Ethylindole Indole, 3-ethyl- (8) 1H-lndole, 3-ethyl- (9) (1484-19-1) 3-Bromo-1-(tert-butyldimethylsilyl)indole 1H-Ind0le, 3-bromo-1-[(l, 1-dimethylethyl)-dimethylsilyl]- (13) (153942-69-9)... 

Medmain, 3-Ethyt-N,N,2-trimethyhlH-indol-5-amine 5-dimethy la mino-3-cthyl-2-iTU thyt indole 3-ethyl-2-methyl -5-dimethylaminoindole 2-methyI -3-ethy1-5-di -methylaminoindole antiserotonin. C (HI8N3 mol wt... 

REGIOSELECTIVE SYNTHESIS OF 3-SUBSTITUTED INDOLES 3-ETHYLINDOLE (IH-Indole, 3-ethyl>]... 

INDOLE -3-ETHYL y3-D-GLUC0 -PYRANOSIDE, AN EXAMPLE OF TRYPTOPHOL GLYCOSIDES... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Another category Ic indole synthesis involves cyclization of a-anilino aldehydes or ketones under the influence of protonic or Lewis acids. This corresponds to retro.synthetic path d in Scheme 4.1. Considerable work on such reactions was done in the early 1960s by Julia and co-workers. The most successful examples involved alkylation of anilines with y-haloacetoacetic esters or amides. For example, heating IV-substituted anilines with ethyl 4-bromoacetoacetate followed by cyclization w ith ZnClj gave indole-3-acetate esterfi]. Additional examples are given in Table 4.3. 

Anomalous Fischer cyclizations are observed with certain c-substituted aryl-hydrazones, especially 2-alkoxy derivatives[l]. The products which are formed can generally be accounted for by an intermediate which w ould be formed by (ip50-substitution during the sigmatropic rearrangement step. Nucleophiles from the reaction medium, e.g. Cl or the solvent, are introduced at the 5-and/or 6-position of the indole ring. Even carbon nucleophiles, e.g. ethyl acetoacelate, can be incorporated if added to the reaction solution[2]. The use of 2-tosyloxy or 2-trifluoromethanesulfonyloxy derivatives has been found to avoid this complication and has proved useful in the preparation of 7-oxygen-ated indoles[3]. 

Ethyl-4-methyl-l-(phenylsulfonyl)indole 4-Ethyl-7-methyl-l-phenylsulfonyl-l,5-dihydropyrano-[3,4-b]pyrrol-5-one phenyl vinyl sulfoxide 60 [3]... 

Indoles can also be alkylated by conjugate addition under alkaline conditions. Under acidic conditions, alkylation normally occurs at C3 (see Section 11.1). Table 9.1 includes examples of alkylation by ethyl acrylate, acrylonitrile, acrylamide and 4-vinylpyridine. 

There are also palladium-catalysed procedures for allylation. Ethyl 3-bromo-l-(4-methylphenylsulfonyl)indole-2-carboxylate is allylated at C3 upon reaction with allyl acetate and hexabutylditin[27], Ihe reaction presumably Involves a ir-allyl-Pd intermediate formed from the allyl acetate, oxidative addition, transmetallation and cross coupling. 

A 20% excess of ethylmagnesium bromide was prepared from magnesium (6.5 g) in ether (80 ml) by adding ethyl bromide (30 g) in ether (30 ml). Indole (25.8 g) in benzene (50 ml) was then added slowly with stirring and stirring was continued for 20 min after addition was complete. A solution of allyl bromide (29.2 g) in benzene (20 ml) was then added slowly. The mixture was stirred overnight and then diluted with ether and the product isolated and purified by distillation (22.7 g, 70% yield). 

Ethyl indole-2-carboxylate 3-(Methoxycarbonyl)propanoyl chloride, AICI3, nitrobenzene 95 [10]... 

Ethyl indole-2-carboxylate 4-Methoxybenzoic acid, TFAA, H3PO4 74 [11]... 

In situ quaternization method ethyl 2-(ethoxycarbonyl)-2-formamido-3-(indol-3-yl)propanoate[7,8J... 

X)ml), The reaction mixture was stirred for 24 h. Nearly all of the solvent was removed in vacuo and the residue dissolved in CH2CI2. The solution was washed with 5% NHj, 1N HCl and brine. The organic layer was dried (NajSOJ and the solvent evaporated in vacuo. The residue was purified by chromatography using CHClj-hexane to give the product (28.0 g, 86%) along with a little 3-[2-nitro-2-(indol-3-ylmethyl)ethyl]indole (2.8 g. 5%). 

A traditional method for such reductions involves the use of a reducing metal such as zinc or tin in acidic solution. Examples are the procedures for preparing l,2,3,4-tetrahydrocarbazole[l] or ethyl 2,3-dihydroindole-2-carbox-ylate[2] (Entry 3, Table 15.1), Reduction can also be carried out with acid-stable hydride donors such as acetoxyborane[4] or NaBHjCN in TFA[5] or HOAc[6]. Borane is an effective reductant of the indole ring when it can complex with a dialkylamino substituent in such a way that it can be delivered intramolecularly[7]. Both NaBH -HOAc and NaBHjCN-HOAc can lead to N-ethylation as well as reduction[8]. This reaction can be prevented by the use of NaBHjCN with temperature control. At 20"C only reduction occurs, but if the temperature is raised to 50°C N-ethylation occurs[9]. Silanes cun also be used as hydride donors under acidic conditions[10]. Even indoles with EW substituents, such as ethyl indole-2-carboxylate, can be reduced[ll,l2]. 

Ethyl indole-2-carboxylate (45.2 g, 0.238 mmol) was dissolved in abs. EtOH (450 ml) in a 11 polyethylene container and cooled in a dry icc-cthanol bath. The solution was saturated with dry HCl gas until the volume increased to 875 ml, Granular tin metal (84.2g, 0.7l0mmol) was added to the slurry and... 

The methine chain is obtained by reacting ethyl o-formate (method A ) or ethylisoformanilide (method B) with a bis quaternary salt of bis-(2-thiazolyllbutane. Concerning dyes with fused thiazolo rings pyrrolo[2. lb]thiazoIe. thiazolo[2.3a]indole. thiazolo[2.3c]1.4-benzox-azine. the a carbon directly linked to the carbon 2 of the thiazoJe ring is also responsible for the classical syntheses giving trimethine or penta-methine dyes. 

Aromatics containing electron releasing groups such as phenols, dim ethyl am in oben 2en e and indole are formylated by 2-ethoxy-l,3-dithiolane in the presence of boron trifluoroetherate, followed by hydrolysis (114). The preformed dithiolanium tetrafluoroborate also undergoes Friedel-Crafts reaction with aromatics such as dim ethyl am in oben 2en e and indole (115), and was used to generate dithiolanium derivatives (formyl precursors) from the enoltrimethylsilyl ether derivatives (116). 

A AlI lation. 1-Substitution is favored when the indole ring is deprotonated and the reaction medium promotes the nucleophilicity of the resulting indole anion. Conditions which typically result in A/-alkylation are generation of the sodium salt by sodium amide in Hquid ammonia, use of sodium hydride or a similar strong base in /V, /V- dim ethyl form am i de or dimethyl sulfoxide, or the use of phase-transfer conditions. 

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