487-89-8

Usage

Uses

Indole-3-carboxaldehyde is used as a biochemical for the preparation of analogs of the indole phytoalexin cyclobrassinin with NR1R2 group. It is also used as the starting material for the synthesis of higher order indoles, including isoindolo[2,1-a]indoles, aplysinopsins, and 4-substituted-tetrahydrobenz[cd]indoles.
Used in Pharmaceutical Industry:
Used in Material Science:
Indole-3-carboxaldehyde can undergo Schiff bases condensation to form multifunctional silica nano-vehicles and magnetic nanoparticles, which have potential applications in various fields, including drug delivery, catalysis, and sensing.

Biosynthesis

Biosynthesis of natural 1H-indole-3-carboxaldehyde was first suggested by Tang and Bonner who reported that, aldehyde[1] was produced via biotransformation of indole-3acetic acid (IAA) using crude enzyme which is prepared from etiolated pea seedlings[10]. On the other hand, brassinin oxidase (BOLm; a fungal detoxifying enzyme) mediates the conversion of the phytoalexin brassinin into 1H-indole3-carboxaldehyde with equivalent ratio[11]. Also, bacteria play an important role in the biosynthesis of it via biotransformation of L-tryptophan using Escherichia coli[12]. 1H-Indole-3-carboxaldhyde and its derivatives are not only the key intermediates for the preparation of biologically active molecules as well indole alkaloids, but also they are important precursors for the synthesis of diverse heterocyclic derivatives.

Synthesis method

Previously, 1H-indole-3-carboxaldehyde has been prepared synthetically either via direct formylation of indole using e.g., Reimer-Tiemann reaction (aq. KOH/CHCl3)[13], Grignard reaction[14], Vilsmeier Haack reaction (POCl3/DMF)[15] or formylation of the potassium salt of indole using carbon monoxide under robust conditions of heat and pressure[16]. Sommelet reaction on gramine and on indole itself oxidation of N-skatyl-N-phenyl-hydroxylamine and/or by hydrolysis of 3-(1,3-dithiolan-2-yl) indole with boron trifluoride diethyl etherate BF3.O(C2H5)2 and mercury (II) oxide HgO. Recently, the researchers developed general and simple approaches by the use of environmentally benign reagents in order to obtain 1H-indole-3-carboxaldyhde, for an example: Unusual oxidation of graminemethiodide [1-(1H-indol-3-yl)-N, N, N-trimethylmethanaminium iodide] using sodium nitrite in N, N-dimethylformamide (DMF) produces it in 68% yield[17]. For another method: Alkaline degradation of ascorbigen leads to a mixture of L-sorbose and L-tagatose derivatives. The later ketoses underwent acetylation and open ring of pyranose using acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) leads to a mixture, which are separated by column chromatography. Deacetylations of compounds mixture have been accompanied by the formation of end product with yield (3%)[18].

Applications for the synthesis of bioactive indole alkaloids

Indole alkaloids constitute a large class of natural products and their diverse and complex structures have been attributed to potent biological activities such as anticancer, anti-inflammatory, antimicrobial, antimalarial, antiplasmodial and protein kinase inhibition. The isolation of bioactive compounds from natural sources is difficult, costly and an extremely time-consuming process, therefore synthetic pathways are more convenient than natural separation to deliver such compounds in considerable amounts. 1H-indole-3-carboxaldehyde is an effective precursor for the synthesis of bioactive indole alkaloids utilizing 1H-indole-3-carboxaldehyde and its derivatives. Phytoalexins Phytoalexins are secondary metabolites formed after plants have been exposed to stressful conditions. The formed compounds constitute an important defense against pathogenic microbes[19]. The common core structure of more than 20 isolated cruciferous phytoalexins is indole possessing a side chain or a heterocycle (fused or linked) containing one or two sulfur atoms[19, 20]. More than twenty phytoalexins have been identified in the family Cruciferae, occurring in many daily used edible vegetables. Chinese cabbage (brassinin, methoxybrassinin, cyclobrassinin, and methoxybrassitin), Japanese radish (brassitin and spirobrassinin), Japanese cabbage (methoxybrassenins A and B), Japanese kohlrabi (cyclobrassinone and methoxyspirobrassinin), Japanese false flax (camalexin) and Indian mustard (brassilexin) are examples of these vegetables[19, 20]. The isolation of indole phytoalexins from cruciferous plants does not provide sufficient quantities for biological screening. Hence, synthetic methods have been elaborated to prepare sufficient quantities of indole phytoalexins including brassinin, cyclobrassinin, brassitin, cyclobrassinone, brassilexin and (S)-(–)-spirobrassinin. A key intermediate in the synthesis of indole phytoalexins is 3-aminomethylindole, which is prepared from indole-3-carboxaldehyde. Bis(indole) Alkaloids: Rhopaladines A–D Four bis (indole) alkaloids, rhopaladines A–D, were isolated from the Okinawan marine tunicate Rhopalaea sp. Rhopaladin B exhibited inhibitory activity against cyclindependent kinase IV and c-ErbB-2 kinase. Rhopaladin C showed antibacterial activity against Sacina lutea and Corynebacterium xerosis[21] Rhopaladines C and D were prepared starting from indole-3-carboxaldehydes. Coscinamides A and B Coscinamides A and B are bis (indole)-containing marine natural products that were isolated from the marine sponge Coscinoderma sp. The preparation of coscinamides A and B started with the protection of 1H-indole-3-carboxaldehyde using Roush’s method[6]. Dipodazine, Isocryptolepine and Dipodazine was isolated and characterized as a major metabolite from Penicillium dipodomyis, and subsequently from meat-associated Penicillium nalgiovese[23]. Dipodazine was synthesized via a stereoselective aldol condensation from N-protected indole-3-carboxaldehyde 1b and 1,4diacetyl-2, 5-piperazinedione in the presence of cesium carbonate[24]. Despite the absence of any biological activity expressed by dipodazine, it has several analogues reported as being active as antifouling agents[22]. Isocryptolepine, an indoloquinoline alkaloid, was isolated from the West African plant Cryptolepis sanguinolenta[25]. The total synthesis of isocryptolepine via a photo-induced cyclization was reported in 2011[25]. The reaction of 1H-indole-3-carboxaldehyde (1a) with aniline in glacial acetic acid afforded the corresponding Schiff base, which is a key step. Carbazole Alkaloids: Mukonine and Clausine E The 1-oxygenated carbazole alkaloids (clausine E, mukonine, and koenoline) were isolated from higher plants of the Rutaceae family. Its synthesis involved an activation and intramolecular cyclization of monoester acids that were obtained via the reaction of 1H-indole-3-carboxaldehyde (1a) with dimethyl succinate and sodium hydride in methanol (Stobbe condensation)[26].

References

Yannai, S. Dictionary of Food Compounds with CD-ROM: Additives, Flavors, and Ingredients; CRC Press: Boca Raton, 2003. Nakajima, E.; Nakano, H.; Yamada, K.; Shigemori, H.; Hasegawa, K. Phytochemistry 2002, 61, 863. El-Sawy, E.; Abo-Salem, H.; Mandour, A. Egypt. J. Chem. 2017, 60, 723. Philip, N. J.; Synder, H. R. Org. Synth. 1959, 39, 30. Dzurilla, M.; Kutschy, P.; Zaletova, J.; Ruzinsky, M.; Kovacik, V. Molecules 2001, 6, 716. Kuramochi, K.; Osada, Y.; Kitahara, T. Tetrahedron 2003, 59, 9447. Wang, Y. Y.; Chen, C. J. Chin. Chem. Soc. 2013, 54, 1363. (a) González-Lamothe, R.; Mitchell, G.; Gattuso, M.; Diarra, M. S.; Malouin, F.; Bouarab, K. Int. J. Mol. Sci. 2009, 10, 3400. (b) Burnett, J. C.; Rossi, J. J. Cell Chem. Biol. 2012, 19, 60. Herrmann, J.; Fayad, A. A.; Mu?ller, R. Nat. Prod. Rep. 2017, 34, 135. Tang Y. U. and Bonner J., The enzymatic inactivation of indole acetic acid. I. Some characteristics of the enzyme contained in pea seedlings, Arch Biochemistry, 13, 25 (1947). Pedras M. S. C., Minic Z. and Sarma-Mamillapalle V. K., Brassinin oxidase mediated transformation of the phytoalexin brassinin: Structure of the elusive co-product, deuterium isotope effect and stereoselectivity, Bioorganic of Medicinal Chemistry,19, 1390 (2011). Chi-Hsinchu H.-T. (TW), US Pat20130273617A1 (2013). Ellinger A. and Flamand C., About synthetically Obtained tryptophan and some of its derivatives, Hoppe-Seyler's, Zeitschrift fur Physiologische Chemie, 55, 8 (1908). British Pat. 618, 638 (1949) (Chem. Abst., 1949, Philip N.J. and Synder H.R., Indole-3-carboxaldhyde, Organic Synthesis, 39, 539 (1959). Tyson F.J. and Shaw J.T., A new approach to 3-indolecarboxaldehyde, Journal of American Chemical Society, 74, 2273 (1952). Sridar V., Maheswari R. and Reddy B. S. R.,An unusual oxidation of gramine methiodides under NaNO2/DMF conditionsIndian, Indian Journal of Chemistry (Section B), 40, 1253 (2001). Lavrenov S. N., Korolev A. M., Reznikova M. I., Sosnov A. V. and Preobrazhenskaya M. N., Study of 1-deoxy-1-(indol-3-yl)-L-sorbose,1deoxy-1-(indol-3-yl)-L-tagatose, and their analogs, Carbohydrate Research, 338, 143 (2003). Pedras, M. S. C.; Nycholat, C. M.; Montaut, S.; Xu, Y.; Khan, A. Q. Phytochemistry 2002, 59, 611. Pedras, M. S. C.; Yaya, E. E.; Glawischnig, E. Nat. Prod. Rep. 2011, 28, 1381. Janosik, T.; Johnson, A.-L.; Bergman, J. Tetrahedron 2002, 58, 2813. Kumar, R. N.; Suresh, T.; Mohan, P. S. Tetrahedron Lett. 2002, 43, 3327. Johnson, A.-L.; Janosik, T.; Bergman, J. ARKIVOC 2002, (viii), 57. Sj?gren, M.; Johnson, A.-L.; Hedner, E.; Dahlstr?m, M.; G?ransson, U.; Shirani, H.; Bergman, J.; Jonsson, P. R.; Bohlin, L. Peptides 2006, 27, 2058. Hingane, D. G.; Kusurkar, R. S. Tetrahedron Lett. 2011, 52, 3686 Budovská, M.; Kutschy, P.; Ko?ár, T.; Gondová, T.; Petrovaj, J. Tetrahedron 2013, 69, 1092.

Synthesis Reference(s)

Journal of the American Chemical Society, 68, p. 1156, 1946 DOI: 10.1021/ja01211a006The Journal of Organic Chemistry, 60, p. 7272, 1995 DOI: 10.1021/jo00127a036Organic Syntheses, Coll. Vol. 4, p. 539, 1963

InChI:InChI=1/C9H7NO/c11-6-7-5-10-9-4-2-1-3-8(7)9/h1-6,10H

Synthetic route

1-(methanesulfonyl)-1H-indole-3-carboxaldehyde (118481-30-4) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran for 1h; Heating;	100%

1-tert-butoxycarbonyl-3-formylindole (57476-50-3) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With potassium phosphate In methanol at 120℃; under 5171.62 Torr; for 0.0333333h; Microwave irradiation;	100%
With sodium carbonate In 1,2-dimethoxyethane; water for 1.5h; Heating;	98%
In various solvent(s) at 150℃; for 0.0833333h; microwave irradiation;	96%

1-acetyl-3-indolylcarbaldehyde (22948-94-3) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With polymer-supported potassium thiophenolate In tetrahydrofuran; methanol at 20℃; for 3h;	99%

1-pivaloyl-1H-indole-3-carbaldehyde → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With lithium diisopropyl amide In tetrahydrofuran; hexane at 40 - 45℃; for 2h;	99%
With n-butyllithium; diisopropylamine In tetrahydrofuran; hexanes at -78 - 45℃; for 2h; Inert atmosphere;	99%

indole (120-72-9) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With trichlorophosphate at 0 - 35℃; for 2.08333h;	98%
With trichlorophosphate at 0 - 55℃; for 2h;	98%
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 2℃; for 0.5h; Vilsmeier-Haack Formylation; Stage #2: indole at 35℃; for 1h; Vilsmeier-Haack Formylation; Stage #3: With water; sodium hydroxide for 0.5h; Reflux;	98%

indole-3-carbinol (700-06-1) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide for 8h; Ambient temperature;	98%
With 1,3,6,8-tetra-n-butylpyrimido<5,4-g>pteridine-2,4,5,7(1H,3H,6H,8H)-tetrone 10-oxide In acetonitrile for 0.0333333h; Irradiation;	90%
With LACTIC ACID; dihydrogen peroxide at 30℃; for 7h;	87%

indole (120-72-9) + formic acid (64-18-6) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With chloro-trimethyl-silane; 4-(trifluoromethyl)benzoic anhydride; silver trifluoromethanesulfonate; titanium tetrachloride In dichloromethane for 20h; Ambient temperature;	88%

1H-indole-3-carboxaldehyde oxime (2592-05-4) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With copper(II) choride dihydrate; water In acetonitrile at 75℃; for 1h;	88%
With iron(III) chloride In N,N-dimethyl-formamide at 25℃; for 0.666667h; sonication;	76%

(3-formylindol-4-yl)thallium (III) bistrifluoroacetate (141692-10-6) + methyl vinyl ketone (78-94-4) → Indole-3-carboxaldehyde (487-89-8) + 4-(3-formylindol-4-yl)-3-buten-2-one

Conditions	Yield
palladium diacetate In N,N-dimethyl-formamide at 120℃;	A n/a B 86%

3-(Dimethylaminomethyl)indole (87-52-5) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With pyridinium chlorochromate In N,N-dimethyl-formamide at 100℃; for 0.5h; Reagent/catalyst;	85%
Stage #1: 3-(Dimethylaminomethyl)indole With iodine; sodium carbonate In 1,4-dioxane at 20℃; for 12h; Stage #2: With water In 1,4-dioxane for 3h; Reagent/catalyst; Solvent;	81%
With hexamethylenetetramine; water; propionic acid
Multi-step reaction with 2 steps 1: PhIO/TMSN3 2: water View Scheme

1-<2-(2-bromophenyl)-1-oxoethyl>-1H-indole-3-carboxaldehyde (171734-95-5) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With dichloro bis(acetonitrile) palladium(II); N-benzyl-N,N,N-triethylammonium chloride In N,N-dimethyl-formamide	85%

N-((1H-indol-3-yl)methyl)aniline (51597-80-9) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With tert.-butylhydroperoxide; ruthenium(III)chloride hydrate; trimethylpyruvic acid In N-methyl-acetamide at 25℃; for 24h; Inert atmosphere;	85%
With tert-Butyl peroxybenzoate; tetra-(n-butyl)ammonium iodide; Trimethylacetic acid In dimethyl sulfoxide at 80℃; for 8h; Inert atmosphere;	70%

1H-indole-3-carboxylic acid (771-50-6) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With D-Glucose; Escherichia coli endogenous alcohol dehydrogenase; Segniliparus rugosus carboxylic acid reductase; dimethyl sulfoxide; magnesium chloride In aq. phosphate buffer at 30℃; for 7h; pH=8; Reagent/catalyst; Enzymatic reaction;	85%
Stage #1: 1H-indole-3-carboxylic acid With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 25℃; Inert atmosphere; Stage #2: With manganese(IV) oxide In acetonitrile at 20℃; Inert atmosphere;
With D-Glucose; Bacillus subtilis glucose dehydrogenase; Segniliparus rugosus carboxylic acid reductase; nicotinamide adenine dinucleotide phosphate; dimethyl sulfoxide; ATP; magnesium chloride In aq. phosphate buffer at 30℃; for 18h; pH=7.5; Enzymatic reaction;
With 2,6-dimethylpyridine; nickel(II) bromide trihydrate; phenylsilane; 4,4'-di-tert-butyl-2,2'-bipyridine; zinc; dimethyl dicarbonate In ethyl acetate at 60℃; for 24h; Schlenk technique; Inert atmosphere;	54 %Chromat.

3-(1,3-dithiolan-2-yl)-1H-indole (36104-60-6) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With boron trifluoride diethyl etherate; water; mercury(II) oxide In tetrahydrofuran for 1h; Ambient temperature;	84%

indole (120-72-9) + N-methylaniline (100-61-8) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With tert-Butyl peroxybenzoate; Trimethylacetic acid In dimethyl sulfoxide at 80℃; for 8h; Inert atmosphere;	82%
With tert.-butylhydroperoxide; ruthenium(III)chloride hydrate; trimethylpyruvic acid In N-methyl-acetamide at 25℃; for 24h; Inert atmosphere; regioselective reaction;	81%

bis(2,2,2-trichloroethyl) 2-(1H-indol-3-yl)-1H-imidazole-1,3(2H)-dicarboxylate → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With water; ammonium chloride; zinc In methanol at 60℃; for 2h;	82%

indole (120-72-9) + isocyanoacetic acid methyl ester (39687-95-1) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → Indole-3-carboxaldehyde (487-89-8) + methyl (Z)-2-(dimethylaminomethyleneamino)-3-<3(1H)-indolyl>acrylate (81467-45-0)

Conditions	Yield
With sodium carbonate; trichlorophosphate In methanol at 25℃; for 24h; (One-pot);	A 9% B 80%

1-(2-azido-ethyl)-1H-indole-3-carbaldehyde (369644-20-2) → Indole-3-carboxaldehyde (487-89-8) + 2,3-dihydro-1H-imidazo[1,2-a]indole-9-carbaldehyde

Conditions	Yield
In various solvent(s) at 180℃;	A 20% B 80%

4-carboxyquinoline 1-oxide (40614-43-5) → Indole-3-carboxaldehyde (487-89-8) + 2-quinolone-4-carboxylic acid (15733-89-8)

Conditions	Yield
In methanol for 0.666667h; Irradiation;	A 6.3% B 79%
In methanol for 0.666667h; Irradiation;	A 6.3% B 79%

indole-3-carbaldehyde dimethylhydrazone → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With pyridinium p-toluenesulfonate; diethylazodicarboxylate In acetonitrile at 60℃; for 11h;	77%

indole (120-72-9) + N,N,N,N,-tetramethylethylenediamine (110-18-9) → Indole-3-carboxaldehyde (487-89-8)

Conditions	Yield
With water; iodine; oxygen; sodium carbonate In 1,4-dioxane at 100℃; under 760.051 Torr; for 36h; Schlenk technique; Sealed tube;	75%
With water; oxygen; potassium iodide In acetonitrile at 25℃; under 750.075 Torr; for 48h; Irradiation;	67%
With water; oxygen; rose bengal; potassium iodide In acetonitrile at 60℃; for 48h; Irradiation;	52%
With potassium carbonate; copper dichloride In acetonitrile for 1h; Reflux;	43%
With water; oxygen; potassium iodide In acetonitrile at 25℃; under 750.075 Torr; for 36h; Irradiation;	35%

Indole-3-carboxaldehyde (487-89-8) + Nitroethane (79-24-3) → 3-(β-nitro-β-methylvinyl)indole (64252-02-4)

Conditions	Yield
With ammonium acetate for 6h; Henry reaction; Reflux;	100%
With ethylenediamine for 3h; Reflux;	95%
With ammonium acetate In benzene Reflux;	94%

Indole-3-carboxaldehyde (487-89-8) + methylamine (74-89-5) → 3-(N-methylformimidoyl)-1H-indole (22980-06-9)

Conditions	Yield
With magnesium sulfate In methanol; dichloromethane for 7h; Heating;	100%
With water
In water 1.) 40 - 45 deg C, 15 min, 2.) room temp., 4 h; Yield given;

Indole-3-carboxaldehyde (487-89-8) → indole-3-carbinol (700-06-1)

Conditions	Yield
With sodium tetrahydroborate In methanol at 0℃; for 1h;	100%
With formic acid In ethanol at 80℃; for 12h; Catalytic behavior;	91%
With ammonia; calcium In tetrahydrofuran at -33℃; for 2h; other reagents: lithium, sodium, liq. ammonia;	80%

Indole-3-carboxaldehyde (487-89-8) + 1-chloro-4-pentyne (14267-92-6) → 1-(4-pentenyl)-1H-indole-3-carboxaldehyde (110206-34-3)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 75℃; for 5h; Alkylation;	100%
With sodium hydride 1.) DMF, 70 deg C, 30 min, 2.) DMF, RT, 1 h; Yield given. Multistep reaction;
With sodium hydride 1.) DMF, RT, 10 min, 2.) DMF, from 70 to 80 deg C, 2 h; Multistep reaction;
Stage #1: 1-chloro-4-pentyne With sodium iodide In N,N-dimethyl-formamide at 20℃; for 0.25h; Inert atmosphere; Stage #2: Indole-3-carboxaldehyde With sodium hydride In N,N-dimethyl-formamide; mineral oil for 48h; Inert atmosphere;

Indole-3-carboxaldehyde (487-89-8) + di-tert-butyl dicarbonate (24424-99-5) → 1-tert-butoxycarbonyl-3-formylindole (57476-50-3)

Conditions	Yield
With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In dichloromethane at 0℃; for 1.83333h; Substitution;	100%
With dmap; triethylamine In dichloromethane at 20℃;	100%
With dmap; triethylamine In dichloromethane at 20℃; for 0.5h; Inert atmosphere;	100%

Indole-3-carboxaldehyde (487-89-8) + ethyl bromoacetate (105-36-2) → (3-formylindol-1-yl)acetic acid ethyl ester (27065-94-7)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 15 - 20℃; for 16.5h;	100%
Stage #1: Indole-3-carboxaldehyde With sodium hydride In N,N-dimethyl-formamide Stage #2: ethyl bromoacetate In N,N-dimethyl-formamide at 20℃; for 16h;	100%
With sodium hydride In DMF (N,N-dimethyl-formamide) at 15 - 20℃; for 16.5h;	100%

Indole-3-carboxaldehyde (487-89-8) + benzyl chloroformate (501-53-1) → N-benzyloxycarbonyl-indole-3-carbaldehyde (74639-50-2)

Conditions	Yield
With dmap; sodium carbonate In water; acetonitrile at 20℃; for 24h;	100%
With triethylamine In tetrahydrofuran 1) 3-5 deg C, 0.5 h; 2) room temperature, 2 h;	96%
Stage #1: Indole-3-carboxaldehyde With triethylamine In dichloromethane at 0 - 20℃; for 1h; Stage #2: benzyl chloroformate In dichloromethane for 18h;	92%

Indole-3-carboxaldehyde (487-89-8) → 3-aminomethylindole (22259-53-6)

Conditions	Yield
Stage #1: Indole-3-carboxaldehyde With hydrogenchloride; ammonia In methanol; water for 5h; Stage #2: With hydrogen; Raney nickel In methanol; water under 3102.97 Torr;	100%
With ammonium acetate; sodium cyanoborohydride; acetic acid
Stage #1: Indole-3-carboxaldehyde With ammonia; ammonium chloride In methanol for 5h; Stage #2: With hydrogen; nickel In methanol; water under 3102.89 Torr;

Indole-3-carboxaldehyde (487-89-8) + acetyl chloride (75-36-5) → 1-acetyl-3-indolylcarbaldehyde (22948-94-3)

Conditions	Yield
With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In dichloromethane Heating;	100%
With triethylamine In dichloromethane for 1h; Acetylation; Heating;	98%
With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In dichloromethane	90%
With triethylamine In tetrahydrofuran at 20℃; for 3h;

Indole-3-carboxaldehyde (487-89-8) + benzyl halide → 1-Benzylindole-3-carboxaldehyde (10511-51-0)

Conditions	Yield
Stage #1: Indole-3-carboxaldehyde With sodium hydride In acetonitrile Stage #2: benzyl halide In acetonitrile	100%
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	87%
With potassium carbonate In acetone Alkylation;	85%

Indole-3-carboxaldehyde (487-89-8) + methyl chloroformate (79-22-1) → 1-methoxycarbonylindole-3-carboxaldehyde (111168-43-5)

Conditions	Yield
With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In dichloromethane Heating;	100%
Stage #1: Indole-3-carboxaldehyde With sodium hydride In acetonitrile; mineral oil at 20℃; for 0.0833333h; Stage #2: methyl chloroformate In acetonitrile; mineral oil for 0.166667h;	85%
Stage #1: Indole-3-carboxaldehyde With sodium hydride In acetonitrile; mineral oil at 20℃; for 0.0833333h; Stage #2: methyl chloroformate In acetonitrile; mineral oil at 20℃; for 0.166667h;	85%

Indole-3-carboxaldehyde (487-89-8) + Ethyl 3-bromopropionate (539-74-2) → 3-(3-formyl-indol-1-yl)-propionic acid ethyl ester (503829-88-7)

Conditions	Yield
With potassium carbonate In acetonitrile for 48h; Heating / reflux;	100%
With potassium carbonate In acetonitrile for 48h; Heating / reflux;	100%
With potassium carbonate In acetonitrile for 48h; Heating / reflux;	100%
With potassium carbonate In acetonitrile for 48h; Heating / reflux;	100%
With potassium carbonate In acetonitrile for 48h;

Indole-3-carboxaldehyde (487-89-8) + 6-hydroxybenzofuran-3-one (6272-26-0) → (2Z)-6-hydroxy-2-(1H-indol-3-ylmethylene)-1-benzofuran-3(2H)-one

Conditions	Yield
With hydrogenchloride In ethanol; water at 75℃; for 5h;	100%
With hydrogenchloride In methanol

Indole-3-carboxaldehyde (487-89-8) + methylamine (74-89-5) → C10H10N2

Conditions	Yield
at 20℃; for 12h;	100%
With sodium sulfate In chloroform at 20℃; for 48h;

Indole-3-carboxaldehyde (487-89-8) + 2,6-dichlorobenzoyl halide → C16H9Cl2NO2 (336187-82-7)

Conditions	Yield
Stage #1: Indole-3-carboxaldehyde With sodium hydride In acetonitrile Stage #2: 2,6-dichlorobenzoyl halide In acetonitrile	100%

Indole-3-carboxaldehyde (487-89-8) + 4-chlorobenzoyl halide → 1-(4-chlorobenzoyl)indole-3-carbaldehyde (62189-77-9)

Conditions	Yield
Stage #1: Indole-3-carboxaldehyde With sodium hydride In acetonitrile Stage #2: 4-chlorobenzoyl halide In acetonitrile	100%

Indole-3-carboxaldehyde (487-89-8) + allyl halide → 1-Allyl-1H-indole-3-carboxaldehyde (111480-86-5)

Conditions	Yield
Stage #1: Indole-3-carboxaldehyde With sodium hydride In acetonitrile Stage #2: allyl halide In acetonitrile	100%
Stage #1: Indole-3-carboxaldehyde With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h; Stage #2: allyl halide In N,N-dimethyl-formamide; mineral oil for 2h;	45%
Stage #1: Indole-3-carboxaldehyde With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 1h; Stage #2: allyl halide In N,N-dimethyl-formamide; mineral oil	45%

Indole-3-carboxaldehyde (487-89-8) + benzoyl halide → 1-benzoyl-1H-indole-3-carbaldehyde (27092-42-8)

Conditions	Yield
Stage #1: Indole-3-carboxaldehyde With sodium hydride In acetonitrile Stage #2: benzoyl halide In acetonitrile	100%
With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In dichloromethane; water

Indole-3-carboxaldehyde (487-89-8) + cinnamyl halide → C18H15NO (1257094-79-3)

Conditions	Yield
Stage #1: Indole-3-carboxaldehyde With sodium hydride In acetonitrile Stage #2: cinnamyl halide In acetonitrile	100%

Upstream product

• 19260-03-8 1-(1H-indol-3-yl)-N,N,N-trimethylmethanaminium methyl sulfate 
• 93-61-8 N-methyl-N-phenylformamide 
• 54-12-6 Trp 
• 36104-60-6 3-(1,3-dithiolan-2-yl)-1H-indole 
• 120-72-9 indole 
• 75258-58-1 C₉H₁₄ClN₅O₂⁽²⁺⁾*2Cl^(1-) 
• 39687-95-1 isocyanoacetic acid methyl ester 
• 68-12-2 N,N-dimethyl-formamide 
• 83-34-1 3-Methylindole 
• 700-06-1 indole-3-carbinol 
• 87-51-4 indole-3-acetic acid 
• 40614-43-5 4-carboxyquinoline 1-oxide 
• 1477-49-2 3-indolylglyoxylic acid 
• 518-06-9 tris(1H-indol-3-yl)methane 

Downstream Products

• 117490-34-3 5-(3-indolylmethylene)hydantoin 
• 10258-18-1 (5Z)-5-((1H-indol-3-yl)methylene)-2-thioxoimidazolidin-4-one 
• 73855-59-1 5-(1H-indol-3-yl-methylene)-2-thioxo-thiazolidin-4-one 
• 42136-84-5 for 3e 
• 24774-42-3 5-(1H-indol-3-ylmethylene)-pyrimidine-2,4,6-trione 
• 64252-02-4 3-(β-nitro-β-methylvinyl)indole 
• 3156-51-2 3-[(E)-2-nitroeth-1-enyl]-1H-indole 
• 1204-06-4 trans-3-indole-acrylic acid 
• 108479-44-3 (Z)-2-(3,4-dimethoxyphenyl)-3-(1H-indol-3-yl)acrylonitrile 
• 102007-39-6 2-(3,4-dimethoxy-phenyl)-4-indol-3-ylmethylen-4H-oxazol-5-one 
• 102883-27-2 1-acetyl-3-(bis-benzoylamino-methyl)-indole 
• 53645-44-6 3ξ-indol-3-yl-2-phenyl-acrylonitrile 
• 76384-45-7 3-<2-(2-Pyridyl)vinyl>indol-methoiodid 
• 73791-25-0 N-indol-3-ylmethylen-anthranilic acid 

Relevant academic research and scientific papers

Triphenylphosphine/1,2-Diiodoethane-Promoted Formylation of Indoles with N, N -Dimethylformamide

Despite intensive studies on the synthesis of 3-formylindoles, it is still highly desirable to develop efficient methods for the formylation of indoles, due to the shortcomings of the reported methods, such as inconvenient operations and/or harsh reaction conditions. Here, we describe a Ph3P/ICH2CH2I-promoted formylation of indoles with DMF under mild conditions. A Vilsmeier-type intermediate is readily formed from DMF promoted by the Ph3P/ICH2CH2I system. A onestep formylation process can be applied to various electron-rich indoles, but a hydrolysis needs to be carried out as a second step in the case of electron-deficient indoles. Convenient operations make this protocol attractive.

Molecular iodine mediated oxidative cleavage of the C-N bond of aryl and heteroaryl (dimethylamino)methyl groups into aldehydes

The oxidative cleavage of the C-N bond of aryl and heteroaryl (dimethylamino)methyl groups is achieved by employing molecular iodine as a mild oxidizing agent under ambient conditions in the presence of a mild base. The important reaction of C3 formylation of free NH and substituted indoles containing various substituents is accomplished from the corresponding Mannich bases. This methodology can also be extended for the synthesis of aryl and other heteroaryl aldehydes and ketones. Furthermore, the usefulness of the method is successfully demonstrated on a gram scale.

A TEMPO-Functionalized Ordered Mesoporous Polymer as a Highly Active and Reusable Organocatalyst

The properties of high stability, periodic porosity, and tunable nature of ordered mesoporous polymers make these materials ideal catalytic nanoreactors. However, their application in organocatalysis has been rarely explored. We report herein for the first time the incorporation of a versatile organocatalyst, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), into the pores of an FDU-type mesoporous polymer via a pore surface engineering strategy. The resulting FDU-15-TEMPO possesses a highly ordered mesoporous organic framework and enhanced stability, and shows excellent catalytic activity in the selective oxidation of alcohols and aerobic oxidative synthesis of 2-substituted benzoxazoles, benzimidazoles and benzothiazoles. Moreover, the catalyst can be easily recovered and reused for up to 7 consecutive cycles.

Hierarchical CeO2@N-C Ultrathin Nanosheets for Efficient Selective Oxidation of Benzylic Alcohols in Water

A monodisperse CeO2@N-C ultrathin nanosheet self-assembled hierarchical structure (USHR) has been prepared by metal-organic framework template methods. The uniform coating of nitrogen-doped carbon (N-C) layers could play an important role in the adsorption and activation of benzylic alcohol. The unique 3D hierarchical structure self-assembled by ultrathin nanosheets provided enough active sites for the catalytic reaction. Therefore, the CeO2@N-C USHR can afford excellent catalytic performance for selective oxidation of benzylic alcohols in water.

First discovery of pimprinine derivatives and analogs as novel potential herbicidal, insecticidal and nematicidal agents

Pimprinine and streptochlorin are indole natural products produced by many species of organisms, and they are reported to possess a wide range of biological activities, such as anticancer, antiviral, antifungal activity and so on. In this study, three series of pimprinine derivatives or analogs were efficiently synthesized under the optimized methods. Biological assays conducted at Syngenta firstly indicated the pimprinine derivatives or analogs possessed potential herbicidal and insecticidal activity, and this is highlighted by compounds 21g, 21h, 21i, 21j, 21l, 22h, 22i and 23h, they possessed significant biological activity as well as broad spectrum. Meanwhile, compounds with benzothiophene-oxazole core (21h, 22h and 23h), showed effective nematicidal activity in primary screening. Compounds 21g and 21i were identified as the most promising lead structures for further study.

Streptochlorin analogues as potential antifungal agents: Design, synthesis, antifungal activity and molecular docking study

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Synthesis, Characterization, and Antioxidant Properties of Novel 1-(4-Aryl-1,3-thiazol-2-yl)-2-{[1-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methylidene}hydrazines

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Cu(II) complexes of 2-indole thiocarbohydrazones: synthesis, characterization and DNA cleavage studies

Abstract: Two Schiff base ligands FT1 and FT2 and their Cu(II) complexes were synthesized and characterized by 1H NMR, ESI-MS, IR, UV-Visible, Fluorescence spectroscopy, EPR and single-crystal X-ray diffraction studies. FT1 crystallizes in the triclinic system while FT2 in the orthorhombic. The DNA cleavage activity of Cu(II) complexes was studied using plasmid pBR322 DNA by gel electrophoresis. All compounds cleave DNA on photoirradiation by oxidative mechanism. Graphic abstract: Two Schiff base ligands FT1 and FT2 and their Cu(II) complexes were synthesized and characterized by 1H NMR, ESI-MS, IR, UV-Visible, Fluorescence spectroscopy, EPR and single-crystal X-ray diffraction studies. Both the Cu(II) complexes of indole thiocarbohydrazones are shown to cleave plasmid pBR322 DNA by oxidative mechanism.[Figure not available: see fulltext.].

Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity

Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3′-ends) in a 2 : 1 stoichiometry.