3- indoles, used

Dimethylaminomethylindole (gramine). Cool 42 5 ml. of aqueous methylamine solution (5 2N ca. 25 per cent, w/v) contained in an 100 ml. flask in an ice bath, add 30 g. of cold acetic acid, followed by 17 -2 g. of cold, 37 per cent, aqueous formaldehyde solution. Pour the solution on to 23 -4 g. of indole use 10 ml. of water to rinse out the flask. Allow the mixture to warm up to room temperature, with occasional shaking as the indole dissolves. Keep the solution at 30-40° overnight and then pour it, with vigorous stirring, into a solution of 40 g. of potassium hydroxide in 300 ml. of water crystals separate. Cool in an ice bath for 2 hours, collect the crystalline solid by suction flltration, wash with three 50 ml. portions of cold water, and dry to constant weight at 50°. The yield of gramine is 34 g. this is quite suitable for conversion into 3-indoleacetic acid. The pure compound may be obtained by recrystaUisation from acetone-hexane m.p. 133-134°. 

Ha.logena.tlon, 3-Chloroindole can be obtained by chlorination with either hypochlorite ion or with sulfuryl chloride. In the former case the reaction proceeds through a 1-chloroindole intermediate (13). 3-Chloroindole [16863-96-0] is quite unstable to acidic aqueous solution, in which it is hydroly2ed to oxindole. 3-Bromoindole [1484-27-1] has been obtained from indole using pytidinium tribromide as the source of electrophilic bromine. Indole reacts with iodine to give 3-iodoindole [26340-47-6]. Both the 3-bromo and 3-iodo compounds are susceptible to hydrolysis in acid but are relatively stable in base. 

Ciamician and Dennstedt reacted the potassium salt of pyrrole with chloroform in ether and isolated, after much purification, 3-chloropyridine, which was confirmed by crystallization with platinum. While the pyrrole salt can be used as the base, the chloroform carbene is typically formed with an alkali alcohol. Forty years later, Robinson and co-workers made 3-chloroquinolines from indoles using the Ciamician-Dennstedt reaction. ... 

Fischer indole condensation of Ni-benzylphenyl-hydrazine and 1-methyl-4-piperidone under the usual acid conditions affords meb-hydroline (29), an indole used as an antihistaminic agent-... 

One year later Van der Eycken and Dehaen described the smooth microwave-assisted borylation of 4, 5, 6 and 7-bromo-lff-indole using PdCl2(dppf) as a precatalyst and KOAc as a base (Scheme 30) [48]. With 5, 6, and 7-bromo-lH-indole, DMSO was used as solvent at a temperature of 150 °C (with a set power of 150 W) for 17-27 min, resulting in the corresponding boronate esters in good yields. For 4-bromo-lH-indole, DME gave a better result at the same temperature (with a set power of 250 W). 

Furthermore, Jana et al. developed a FeCl3-catalyzed C3-selective Friedel-Crafts alkylation of indoles, using allylic, benzylic, and propargylic alcohols in nitromethane as solvent at room temperature. This method can also be used for the alkylation of pyrrole (Scheme 4). The reactions were complete within 2-3 h without the need of an inert gas atmosphere leading to the C-3-substitution product exclusively in moderate to good yields [20]. 

The same group also developed an efficient entry to indoles using a combination of a hydroformylation and a Fischer indole synthesis [212]. Under optimized condi-... 

Scheme 13.3 Pattern of deuteration at different sites for indole using various solvents and microwave irradiation.

A similar strategy enabled the 2-alkenylation of indoles using catalytic palladium chemistry (Equation (139)).121... 

A -Sulphonylation of pyrroles and indoles, using a liquidtliquid two-phase procedure [3, 48, 50-54], is superior to the traditional methods, which frequently require preformation of the heteroaryl sodium derivative, whereas A-sulphonylation of indole using a sulphonyl chloride in the presence of pyridine leads to the formation of the l,4-dihydro-4-indol-3-ylpyridine [49], The liquid liquid two-phase procedure outlined below is suitable for most A -Sulphonylation reactions with heteroaromatic compounds, but it is sometimes advisable to add a second quantity of the sulphonyl chloride during the course of the reaction [22,47]. 

Novel Synthesis of Quinolines and Indoles Using Ring Closing Metathesis... 

Fig. 6.54. El mass spectrum of indole. Used by permission of NIST. NIST 2002.

Scheme 22. ARO of enantiomerically pure epoxide with various indoles using catalyst 51.

Scheme 65 Alkylation of indoles using a chiral anion/chrral amine combination...

Flouk has also considered the alkylation reactions of pyrroles and indoles using the same class of catalyst. The report addresses the fact that while catalyst 12 provides high ees in the alkylation of pyrroles (Scheme 15), the same is not true of indoles and catalyst 21 is required instead (Scheme 16). A thorough examination of the accessible transition states for the reaction of iminium ion 184 with pyrrole and with indole led to the conclusion that the two reactions occur through different transition states. Pyrrole adopts a closed transition state reminiscent of that of the Diels-Alder reaction whereas indole adopts an open transition state (Fig. 19) [233]. 

In one of the few publications not directly connected with the synthesis of alkaloids, an original method for the formation of hexahydroazocino[4,3-fc]-indoles using a Mannich intermolecular reaction of the corresponding 2-(N-i -aminobutyl)indoles 50 has been reported (Scheme 14 87JCS(P1)1599). 

Table 2.5 Asymmetric hydrogenation of indoles using (S,S)-(I ,I )-PhTRAP-rhodium complex as catalyst...

Fagnola, M. C. Candiani, I. Visentin, G. Cabri, W. Zarini, F. Mongelli, N. Bedeschi, A. Solid-Phase Synthesis of Indoles Using the Palladium-Catalysed Coupling of Alkynes with Iodoaniline Derivatives, Tetrahedron Lett. 1997, 38, 2307-2310. 

Nitroalkenes react enantioselectively (ee usually 40%) with indoles using chiral hydrogen-bonding bis-sulfonamides as catalysts [e.g. to form (41)].44 An enantioselective reaction (usually ee 83-95%) has been shown to occur between indoles and ethyl ... 

Synthesis of Phosphorus-containing Indoles Using Organophosphorus Compounds with Active Methylene Group... 

For recent reports and reviews on the synthesis of indoles using palladium, see ... 

In the initial phases of this effort a means for introducing appropriate functionality in the C-l/C-2 positions from an unsubstituted precursor such as 80 that would eventually lead to an aziridine ring in the final target compound(s) was needed. When considering the oxidation of simple hexahydro-8-oxo-1 //-pyrrolo[ 1,2-a] indoles using DDQ, two mechanistic pathways are possible leading to either of the carbocationic intermediates 81 or 82 via hydride abstraction at C-5 or C-1, respectively (Scheme 12).69 Proton loss from 81 would ultimately lead to the phenolic product 83 whereas nucleophilic trapping of intermediate 82 by alcohols would afford the C-l-substituted ethers 84. Oxidative transformations at... 

The enantioselective reactions of indoles using alkylidene malonates gave the alkylation products 92 in excellent yield and with moderate ee. 

Most recently, Wagaw, Yang, and Buchwald published a full account of the synthesis of indoles using the palladium-catalyzed amination process [185]. From the standpoint of catalysis, new results included improved turnover numbers and rates when Xantphos was used as ligand. Moreover, this ligand allowed diarylation of the hydrazone, including a one-pot sequential diarylation to provide mixed diaryl hydrazones. A procedure for the alkylation of N-aryl hydrazones was also reported. These procedures allow the formation of N-aryl and N-alkyl indoles after subjecting the products to Fischer conditions for indole synthesis. 

---