Indole-2-carbaldehyde

The possibility of activating the indole nucleus to nucleophilic substitution has been realized by formation of chromium tricarbonyl complexes. For example, the complex from TV-methylindole (215) undergoes nucleophilic substitution with 2-lithio-l,3-dithiane to give a product (216) which can be transformed into l-methylindole-7-carbaldehyde (217) (78CC1076). 

Dicarbonylimidazole reacted with the anthranilic acid derivative (498) to produce the fused isoxazolone IV-oxide (499) (77ZOR462). Methyl nitroacetate reacted with indole-3-carbaldehyde to produce (500) (70KGS1505). Treatment of (501) with base gave 3,4,5-triphenyl-2-isoxazoline IV-oxide (Scheme 142) (69JOC984). The reaction was reported to be a direct displacement as (502) did not give a product and no incorporation of deuterium was found using DOMe. 

Indole-7-carbaldehyde, 1-methyl-synthesis, 4, 83 Indole-3-carbaldehydes synthesis, 2, 251 Indole-2-carboxamide reduction, 4, 256 synthesis, 4, 360 Indole-3-carboxamide synthesis, 4, 347... 

This trend is also observed in the reactions with nitrogen- and carbon-centered nucleophiles (2001H425). Thus, the reaction of 109 with sodium indolyl in DMF affords methyl 2-(indol-l-yl)indole-3-carboxylate (188, 77%). In better yield, 2-(indol-l-yl)indole-3-carbaldehyde (189, 95%) is formed in the corresponding reaction (99H1157) of 115a (Scheme 28). Sodium imidazolyl reacts with 109 in DMF at 60°C to afford methyl 2-(imidazol-l-yl)indole-3-carboxylate (190,28%), methyl indole-3-carboxylate (191,11 %), and unreacted 109 (36%). In contrast, under the same conditions, 110 and 115a provide higher yields of methyl 2-(imidazol-... 

Thus, reaction of a mixture of the E- and Z-isomers 986 with LDA, followed by addition of DMF, afforded the 3-[(E)-2-methoxyethenyl]indole-2-carbaldehyde (987)... 

Vilsmeier reaction of 2-oxindole (830) afforded 2-chloroindole-3-carbaldehyde (891). Suzuki cross-coupling of 891 with furan-3-boronic acid (1124), followed by protection of the indole nitrogen with benzyloxymethyl (BOM) chloride, led to... 

Nitroso derivatives (120) are obtained from indoles they exist largely in oximino forms (121) (80IJC(B)767). The N-nitrosation of 5-chloroindole is followed by a migration of the nitroso group from N to C-3, to give an indolenine-3-oxime (122) hydrolysis and recyclization leads to a indazole carbaldehyde (123) (86JA4115). 

The reaction of pyrrole with dichlorocarbene, generated from chloroform and strong base, gives a bicyclic intermediate which can be transformed to either 3-chloropyridine (155) or pyrrole-2-carbaldehyde (156). Indole gives a mixture of 3-chloroquinoline (157) and indole-3-carbaldehyde (158). The optimum conditions involve phase transfer (76S249, 76S798). Benzofuran reacts with dichlorocarbene in hexane solution to give the benzopyran (159), whereas benzothiophene fails to react. 

A second type of route from pyrroles to indoles involves construction of a vinylpyrrole suitable for [4 + 2] cycloaddition leading to a dihydro- or tetrahydro-indole (Scheme 19) (80JOC4515, 81T1597). The dihydro systems can be easily aromatized. 2-Nitrovinylpyrroles, which are readily available by condensation of pyrrole-2-carbaldehyde with nitromethane, give fully aromatic indoles on reaction with dienophiles (equation 139) (73JCS(P1)2450). The aromatization results from elimination of nitrous acid and a further dehydrogenation. 

Indole and various 2-substituted indoles give the 3-formyl derivative in generally excellent yields under Vilsmeier-Haack conditions (79HC(25-3)357, B-70MI30609). 3-Methylindole gives the 2-carbaldehyde, but in rather poor yield (63JPS645). 

Thallation of l-methoxyindole-3-carbaldehyde with thallium trisfluo-roacetate followed by treatment with potassium iodide gave the 4-iodo derivative in 91% yield, and this has been converted into many other 1-methoxyindole derivatives (86CPB677). When the thallated indole reacted with methyl acrylate in the presence of a catalytic quantity of pal-ladium(ll) acetate, 47% of the product was the 4-derivative 160, but 11% of the 5-isomer was also formed (86CPB4116). 

Base-catalyzed condensation (Equation 31) of 4,6-dinitro-l-tosylindoline with salicylaldehyde or 2-hydroxy-naphthalene-l-carbaldehyde is accompanied by intramolecular nucleophilic substitution for one of the nitro groups to give benzo- and naphthooxepino[4,3,2-crf indoles, respectively <2003IZV725>. 

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