Indole

Indole is a solid at room temperature. It occurs naturally in human feces and has an intense fecal odor. At very low concentrations, however, it has a flowery smell,{{cite web | last1=Purves | first1=Dale | last2=Augustine | first2=George J | last3=Fitzpatrick | first3=David | last4=Katz | first4=Lawrence C | last5=LaMantia | first5=Anthony-Samuel | last6=McNamara | first6=James O | last7=Williams | first7=S Mark | title=Olfactory Perception in Humans | website=Olfactory Perception in Humans | url=https://www.ncbi.nlm.nih.gov/books/NBK11032/ | access-date=20 October 2020}} and is a constituent of many perfumes. It also occurs in coal tar. It has been identified in cannabis.{{Cite journal |last1=Oswald |first1=Iain W. H. |last2=Paryani |first2=Twinkle R. |last3=Sosa |first3=Manuel E. |last4=Ojeda |first4=Marcos A. |last5=Altenbernd |first5=Mark R. |last6=Grandy |first6=Jonathan J. |last7=Shafer |first7=Nathan S. |last8=Ngo |first8=Kim |last9=Peat |first9=Jack R. |last10=Melshenker |first10=Bradley G. |last11=Skelly |first11=Ian |last12=Koby |first12=Kevin A. |last13=Page |first13=Michael F. Z. |last14=Martin |first14=Thomas J. |date=2023-10-12 |title=Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of Exotic Cannabis |journal=ACS Omega |volume=8 |issue=42 |pages=39203–39216 |language=en |doi=10.1021/acsomega.3c04496 |pmid=37901519 |pmc=10601067 |issn=2470-1343|doi-access=free }} It is the main volatile compound in stinky tofu.{{cite journal |last1=Liu |first1=Yuping |last2=Miao |first2=Zhiwei |last3=Guan |first3=Wei |last4=Sun |first4=Baoguo |title=Analysis of Organic Volatile Flavor Compounds in Fermented Stinky Tofu Using SPME with Different Fiber Coatings |journal=Molecules |date=26 March 2012 |volume=17 |issue=4 |pages=3708–3722 |doi=10.3390/molecules17043708 |pmid=22450681 |pmc=6268145 |doi-access=free }}

When indole is a substituent on a larger molecule, it is called an indolyl group by systematic nomenclature.

Indole undergoes electrophilic substitution, mainly at position 3 (see diagram in right margin). Substituted indoles are structural elements of (and for some compounds, the synthetic precursors for) the tryptophan-derived tryptamine alkaloids, which includes the neurotransmitter serotonin and the hormone{{cite journal |last1=Lee |first1=Jung Goo |title=The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease |journal=Brain Sciences |date=21 October 2019 |volume=9 |issue=285 |page=285 |doi=10.3390/brainsci9100285 |pmid=31640239 |pmc=6826722 |doi-access=free }} melatonin, as well as the naturally occurring psychedelic drugs dimethyltryptamine and psilocybin. Other indolic compounds include the plant hormone auxin (indolyl-3-acetic acid, IAA), tryptophol, the anti-inflammatory drug indomethacin, and the betablocker pindolol.

The name indole is a portmanteau of the words indigo and oleum, since indole was first isolated by treatment of the indigo dye with oleum.

File:Baeyer indole structure.png

Indole chemistry began to develop with the study of the dye indigo. Indigo can be converted to isatin and then to oxindole. Then, in 1866, Adolf von Baeyer reduced oxindole to indole using zinc dust.{{cite journal|author-link = Adolf von Baeyer|last=Baeyer |first=A.|journal = Annalen der Chemie und Pharmacie|year = 1866|volume = 140|pages = 295–296|doi = 10.1002/jlac.18661400306|title = Ueber die Reduction aromatischer Verbindungen mittelst Zinkstaub|trans-title=On the reduction of aromatic compounds by means of zinc dust|issue = 3|url=https://archive.org/stream/annalenderchemi11liebgoog#page/n690/mode/2up}} In 1869, he proposed a formula for indole.{{cite journal|author-link = Adolf von Baeyer|last1=Baeyer |first1=A. |last2=Emmerling |first2=A.|journal = Berichte der Deutschen Chemischen Gesellschaft|year = 1869|volume = 2|pages = 679–682|doi = 10.1002/cber.186900201268|title = Synthese des Indols|trans-title=Synthesis of indole|url=http://babel.hathitrust.org/cgi/pt?id=uc1.b3481747;view=1up;seq=709}}

Certain indole derivatives were important dyestuffs until the end of the 19th century. In the 1930s, interest in indole intensified when it became known that the indole substituent is present in many important alkaloids, known as indole alkaloids (e.g., tryptophan and auxins), and it remains an active area of research today.{{cite journal|first1=R. B. |last1=Van Order |first2=H. G. |last2=Lindwall |journal = Chem. Rev.|year = 1942|volume = 30|pages = 69–96|doi = 10.1021/cr60095a004|title = Indole}}

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Indole is biosynthesized in the shikimate pathway via anthranilate.{{Lehninger4th}} It is an intermediate in the biosynthesis of tryptophan, where it stays inside the tryptophan synthase molecule between the removal of 3-phospho-glyceraldehyde and the condensation with serine. When indole is needed in the cell, it is usually produced from tryptophan by tryptophanase.{{Cite book|url=https://books.google.com/books?id=9mGzkso4NVQC&pg=PA251|title=Metabolic Engineering: Principles and Methodologies|last1=Stephanopoulos|first1=George|last2=Aristidou|first2=Aristos A.|last3=Nielsen|first3=Jens|date=1998-10-17|publisher=Academic Press|isbn=9780080536286|pages=251|language=en}}

:File:Tryptophan biosynthesis (en).svg{{clear left}}

As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence.{{cite journal|last1=Lee|first1=Jin-Hyung|last2=Lee|first2=Jintae|title=Indole as an intercellular signal in microbial communities|journal=FEMS Microbiology Reviews|volume=34|issue=4|pages=426–44|year=2010|issn=0168-6445|doi=10.1111/j.1574-6976.2009.00204.x|pmid=20070374|doi-access=free}} A number of indole derivatives have important cellular functions, including neurotransmitters such as serotonin.

{{Tryptophan metabolism by human microbiota|align=left}}

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Common classical methods applied for the detection of extracellular and environmental indoles, are Salkowski, Kovács, Ehrlich’s reagent assays and HPLC.{{Cite journal |last=Ehmann |first=Axel |date=1977-02-11 |title=The van URK-Salkowski reagent — a sensitive and specific chromogenic reagent for silica gel thin-layer chromatographic detection and identification of indole derivatives |url=https://www.sciencedirect.com/science/article/pii/S0021967300893000 |journal=Journal of Chromatography A |language=en |volume=132 |issue=2 |pages=267–276 |doi=10.1016/S0021-9673(00)89300-0 |pmid=188858 |issn=0021-9673}}{{Cite journal |last1=Darkoh |first1=Charles |last2=Chappell |first2=Cynthia |last3=Gonzales |first3=Christopher |last4=Okhuysen |first4=Pablo |date=December 2015 |editor-last=Schloss |editor-first=P. D. |title=A Rapid and Specific Method for the Detection of Indole in Complex Biological Samples |journal=Applied and Environmental Microbiology |language=en |volume=81 |issue=23 |pages=8093–8097 |doi=10.1128/AEM.02787-15 |issn=0099-2240 |pmc=4651089 |pmid=26386049|bibcode=2015ApEnM..81.8093D }}{{Cite journal |last1=Gilbert |first1=Sarah |last2=Xu |first2=Jenny |last3=Acosta |first3=Kenneth |last4=Poulev |first4=Alexander |last5=Lebeis |first5=Sarah |last6=Lam |first6=Eric |date=2018 |title=Bacterial Production of Indole Related Compounds Reveals Their Role in Association Between Duckweeds and Endophytes |journal=Frontiers in Chemistry |volume=6 |page=265 |doi=10.3389/fchem.2018.00265 |issn=2296-2646 |pmc=6052042 |pmid=30050896 |bibcode=2018FrCh....6..265G |doi-access=free }} For intracellular indole detection and measurement genetically encoded indole-responsive biosensor is applicable.{{Cite journal |last1=Matulis |first1=Paulius |last2=Kutraite |first2=Ingrida |last3=Augustiniene |first3=Ernesta |last4=Valanciene |first4=Egle |last5=Jonuskiene |first5=Ilona |last6=Malys |first6=Naglis |date=January 2022 |title=Development and Characterization of Indole-Responsive Whole-Cell Biosensor Based on the Inducible Gene Expression System from Pseudomonas putida KT2440 |journal=International Journal of Molecular Sciences |language=en |volume=23 |issue=9 |pages=4649 |doi=10.3390/ijms23094649 |issn=1422-0067 |pmc=9105386 |pmid=35563040 |doi-access=free }}

Indoles and their derivatives are promising against tuberculosis, malaria, diabetes, cancer, migraines, convulsions, hypertension, bacterial infections of methicillin-resistant Staphylococcus aureus (MRSA) and even viruses.{{cite journal |last1=Ramesh |first1=Deepthi |last2=Joji |first2=Annu |last3=Vijayakumar |first3=Balaji Gowrivel |last4=Sethumadhavan |first4=Aiswarya |last5=Mani |first5=Maheswaran |last6=Kannan |first6=Tharanikkarasu |title=Indole chalcones: Design, synthesis, in vitro and in silico evaluation against Mycobacterium tuberculosis |journal=European Journal of Medicinal Chemistry |date=15 July 2020 |volume=198 |pages=112358 |doi=10.1016/j.ejmech.2020.112358 |pmid=32361610 |s2cid=218490655 |language=en |issn=0223-5234|doi-access=free }}{{cite journal |last1=Qin |first1=Hua-Li |last2=Liu |first2=Jing |last3=Fang |first3=Wan-Yin |last4=Ravindar |first4=L. |last5=Rakesh |first5=K. P. |title=Indole-based derivatives as potential antibacterial activity against methicillin-resistance Staphylococcus aureus (MRSA) |journal=European Journal of Medicinal Chemistry |date=15 May 2020 |volume=194 |pages=112245 |doi=10.1016/j.ejmech.2020.112245 |pmid=32220687 |s2cid=214695328 |url=https://doi.org/10.1016/j.ejmech.2020.112245 |language=en |issn=0223-5234}}{{cite journal |last1=Thanikachalam |first1=Punniyakoti Veeraveedu |last2=Maurya |first2=Rahul Kumar |last3=Garg |first3=Vishali |last4=Monga |first4=Vikramdeep |title=An insight into the medicinal perspective of synthetic analogs of indole: A review |journal=European Journal of Medicinal Chemistry |date=15 October 2019 |volume=180 |pages=562–612 |doi=10.1016/j.ejmech.2019.07.019 |pmid=31344615 |s2cid=198911553 |url=https://doi.org/10.1016/j.ejmech.2019.07.019 |language=en |issn=0223-5234}}{{cite journal |last1=Kumari |first1=Archana |last2=Singh |first2=Rajesh K. |title=Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives |journal=Bioorganic Chemistry |date=1 August 2019 |volume=89 |pages=103021 |doi=10.1016/j.bioorg.2019.103021 |pmid=31176854 |s2cid=182950054 |url=https://doi.org/10.1016/j.bioorg.2019.103021 |language=en |issn=0045-2068}}{{cite journal |last1=Jia |first1=Yanshu |last2=Wen |first2=Xiaoyue |last3=Gong |first3=Yufeng |last4=Wang |first4=Xuefeng |title=Current scenario of indole derivatives with potential anti-drug-resistant cancer activity |journal=European Journal of Medicinal Chemistry |date=15 August 2020 |volume=200 |pages=112359 |doi=10.1016/j.ejmech.2020.112359 |pmid=32531682 |s2cid=219021072 |url=https://doi.org/10.1016/j.ejmech.2020.112359 |language=en |issn=0223-5234}}

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Indole and its derivatives can also be synthesized by a variety of methods.{{cite journal|last = Gribble|first= G. W.|journal = J. Chem. Soc. Perkin Trans. 1 |year = 2000|doi = 10.1039/a909834h|title = Recent developments in indole ring synthesis—methodology and applications|page = 1045|issue = 7}}{{cite journal|last1=Cacchi |first1=S. |last2=Fabrizi |first2=G. |journal = Chem. Rev.|doi = 10.1021/cr040639b|pmid = 16011327|title = Synthesis and Functionalization of Indoles Through Palladium-catalyzed Reactions|year = 2005|volume = 105|issue = 7|pages = 2873–2920|hdl=11573/232340 }}{{cite journal|last1=Humphrey |first1=G. R. |last2=Kuethe |first2=J. T. |journal = Chem. Rev.|doi = 10.1021/cr0505270|pmid = 16836303|title = Practical Methodologies for the Synthesis of Indoles|year = 2006|volume = 106|issue = 7|pages = 2875–2911}}

The main industrial routes start from aniline via vapor-phase reaction with ethylene glycol in the presence of catalysts:

:File:Indole from aniline and ethylene glycol 2.svg and ethylene glycol to give indole.]]

In general, reactions are conducted between 200 and 500 °C. Yields can be as high as 60%. Other precursors to indole include formyltoluidine, 2-ethylaniline, and 2-(2-nitrophenyl)ethanol, all of which undergo cyclizations.{{Ullmann|first1=Gerd |last1=Collin |first2=Hartmut |last2=Höke |title=Indole |doi=10.1002/14356007.a14_167}}

{{main|Leimgruber–Batcho indole synthesis}}

:File:Leimgruber-Batcho Indole Scheme.png

The Leimgruber–Batcho indole synthesis is an efficient method of synthesizing indole and substituted indoles.{{Cite web|url=https://nsp-sun.com/wp-content/uploads/2020/02/indol.pdf|title=Indol NSP}} Originally disclosed in a patent in 1976, this method is high-yielding and can generate substituted indoles. This method is especially popular in the pharmaceutical industry, where many pharmaceutical drugs are made up of specifically substituted indoles.

{{main|Fischer indole synthesis}}

:File:Fischer indole reaction scheme.svg

File:One-pot synthesis of indoles.svg

One of the oldest and most reliable methods for synthesizing substituted indoles is the Fischer indole synthesis, developed in 1883 by Emil Fischer. Although the synthesis of indole itself is problematic using the Fischer indole synthesis, it is often used to generate indoles substituted in the 2- and/or 3-positions. Indole can still be synthesized, however, using the Fischer indole synthesis by reacting phenylhydrazine with pyruvic acid followed by decarboxylation of the formed indole-2-carboxylic acid. This has also been accomplished in a one-pot synthesis using microwave irradiation.{{cite journal|last1=Bratulescu|first1=George|title=A new and efficient one-pot synthesis of indoles|journal=Tetrahedron Letters|volume=49|page=984|year=2008|doi=10.1016/j.tetlet.2007.12.015|issue=6 }}

• Bartoli indole synthesis
• Bischler–Möhlau indole synthesis
• Cadogan-Sundberg indole synthesis
• Fukuyama indole synthesis
• Gassman indole synthesis
• Hemetsberger indole synthesis
• Larock indole synthesis
• Madelung synthesis
• Nenitzescu indole synthesis
• Reissert indole synthesis
• Baeyer–Emmerling indole synthesis
• In the Diels–Reese reaction{{cite journal|doi = 10.1002/jlac.19345110114|journal = Justus Liebig's Annalen der Chemie|title = Synthesen in der hydroaromatischen Reihe. XX. Über die Anlagerung von Acetylen-dicarbonsäureester an Hydrazobenzol|trans-title=Syntheses in the hydroaromatic series. XX. The addition of acetylene dicarboxylic acid ester to hydrazobenzene|year = 1934|last1 = Diels |first1=Otto|volume = 511|page = 168|last2 = Reese|first2 = Johannes}}{{cite journal|title = An Extension of the Diels-Reese Reaction|first1=Ernest H. |last1=Huntress |first2=Joseph |last2=Bornstein |first3=William M. |last3=Hearon |journal = J. Am. Chem. Soc.|doi = 10.1021/ja01591a055|year = 1956|volume = 78|page = 2225|issue = 10|bibcode=1956JAChS..78.2225H }} dimethyl acetylenedicarboxylate reacts with 1,2-diphenylhydrazine to an adduct, which in xylene gives dimethyl indole-2,3-dicarboxylate and aniline. With other solvents, other products are formed: with glacial acetic acid a pyrazolone, and with pyridine a quinoline.

Unlike most amines, indole is not basic: just like pyrrole, the aromatic character of the ring means that the lone pair of electrons on the nitrogen atom is not available for protonation.{{Cite book|url=https://books.google.com/books?id=RrKgfuRwsqsC&pg=PA143|title=Essentials of Organic Chemistry: For Students of Pharmacy, Medicinal Chemistry and Biological Chemistry|last=Dewick|first=Paul M.|date=2013-03-20|publisher=John Wiley & Sons|isbn=9781118681961|pages=143|language=en}} Strong acids such as hydrochloric acid can, however, protonate indole. Indole is primarily protonated at the C3, rather than N1, owing to the enamine-like reactivity of the portion of the molecule located outside of the benzene ring. The protonated form has a pK_a of −3.6. The sensitivity of many indolic compounds (e.g., tryptamines) under acidic conditions is caused by this protonation.

The most reactive position on indole for electrophilic aromatic substitution is C3, which is 10¹³ times more reactive than benzene. For example, it is alkylated by phosphorylated serine in the biosynthesis of the amino acid tryptophan. Vilsmeier–Haack formylation of indole{{cite journal|last1=James |first1=P. N. |last2=Snyder |first2=H. R. |year=1959|title=Indole-3-aldehyde |journal=Organic Syntheses|volume=39|page=30| url=http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0539|doi=10.15227/orgsyn.039.0030}} will take place at room temperature exclusively at C3.

:File:Indole Vilsmeyer-Haack Formylation.png

Since the pyrrolic ring is the most reactive portion of indole, electrophilic substitution of the carbocyclic (benzene) ring generally takes place only after N1, C2, and C3 are substituted. A noteworthy exception occurs when electrophilic substitution is carried out in conditions sufficiently acidic to exhaustively protonate C3. In this case, C5 is the most common site of electrophilic attack.{{cite journal |last1=Noland |first1=W. E. |last2=Rush |first2=K. R. |last3=Smith |first3=L. R. |year=1966 |title=Nitration of Indoles. IV. The Nitration of 2-Phenylindole. |journal=J. Org. Chem. |volume=31 |pages=65–69 |doi=10.1021/jo01339a013}}

Gramine, a useful synthetic intermediate, is produced via a Mannich reaction of indole with dimethylamine and formaldehyde. It is the precursor to indole-3-acetic acid and synthetic tryptophan.

:File:Gramine From Indole Scheme.png

The N–H center has a pK_a of 21 in DMSO, so that very strong bases such as sodium hydride or n-butyl lithium and water-free conditions are required for complete deprotonation. The resulting organometalic derivatives can react in two ways. The more ionic salts such as the sodium or potassium compounds tend to react with electrophiles at nitrogen-1, whereas the more covalent magnesium compounds (indole Grignard reagents) and (especially) zinc complexes tend to react at carbon 3 (see figure below). In analogous fashion, polar aprotic solvents such as DMF and DMSO tend to favour attack at the nitrogen, whereas nonpolar solvents such as toluene favour C3 attack.{{cite journal|last1=Ahmad |first1=Shabee |last2= |first2= |year=2025|title=Indole Derivatives as Anticancer Agent: Recent Developments |journal=JioaVatar|volume=|page=| url=https://jioavatar.com/a1|doi=}}{{cite journal|last1=Heaney |first1=H. |last2=Ley |first2=S. V. |year=1974|title=1-Benzylindole |journal=Organic Syntheses|volume=54|page=58| url=http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0104|doi=10.15227/orgsyn.054.0058}}

:File:Indole anion reactions.svg

After the N–H proton, the hydrogen at C2 is the next most acidic proton on indole. Reaction of N-protected indoles with butyl lithium or lithium diisopropylamide results in lithiation exclusively at the C2 position. This strong nucleophile can then be used as such with other electrophiles.

:File:Bergman Indole Lithiation.png

Bergman and Venemalm developed a technique for lithiating the 2-position of unsubstituted indole,{{cite journal|author1=Bergman, J. |author2=Venemalm, L. |journal = J. Org. Chem.|doi = 10.1021/jo00034a058|title = Efficient synthesis of 2-chloro-, 2-bromo-, and 2-iodoindole|year = 1992|volume = 57|page = 2495|issue = 8}} as did Katritzky.{{cite journal|title = Facile Synthesis of 2-Substituted Indoles and Indolo[3,2-b]carbazoles from 2-(Benzotriazol-1-ylmethyl)indole|first1=Alan R. |last1=Katritzky |first2=Jianqing |last2=Li |first3=Christian V. |last3=Stevens |journal = J. Org. Chem.|year = 1995|volume = 60|issue = 11|pages = 3401–3404|doi = 10.1021/jo00116a026}}

Due to the electron-rich nature of indole, it is easily oxidized. Simple oxidants such as N-bromosuccinimide will selectively oxidize indole 1 to oxindole (4 and 5).

:File:Indole NBS Oxidation.png

Only the C2–C3 pi bond of indole is capable of cycloaddition reactions. Intramolecular variants are often higher-yielding than intermolecular cycloadditions. For example, Padwa et al.{{cite journal|last1=Lynch |first1=S. M. |last2=Bur |first2=S. K. |last3=Padwa |first3=A. |journal = Org. Lett.|doi = 10.1021/ol027024q|pmid = 12489950|title = Intramolecular Amidofuran Cycloadditions across an Indole π-Bond: An Efficient Approach to the Aspidosperma and Strychnos ABCE Core|year = 2002|volume = 4|issue = 26|pages = 4643–5}} have developed this Diels-Alder reaction to form advanced strychnine intermediates. In this case, the 2-aminofuran is the diene, whereas the indole is the dienophile. Indoles also undergo intramolecular [2+3] and [2+2] cycloadditions.

:File:Indole Cycloaddition Padwa.png

Despite mediocre yields, intermolecular cycloadditions of indole derivatives have been well documented.{{Cite journal| pages = 1797–1842| year = 1995| doi = 10.1021/cr00038a004| last2 = Cook| last1 = Cox| volume = 95 | first1 = E. D.| journal = Chemical Reviews| first2 = J. M.| title = The Pictet-Spengler condensation: a new direction for an old reaction| issue = 6}}{{cite journal |last1=Gremmen |first1=C. |last2=Willemse |first2=B. |last3=Wanner |first3=M. J. |last4=Koomen |first4=G.-J. | journal = Org. Lett. | volume = 2 | year = 2000 | pages = 1955–1958 | doi = 10.1021/ol006034t | title = Enantiopure Tetrahydro-β-carbolines via Pictet–Spengler Reactions with N-Sulfinyl Tryptamines | issue = 13|pmid=10891200 }}{{cite journal|title=The intermolecular Pictet–Spengler condensation with chiral carbonyl derivatives in the stereoselective syntheses of optically-active isoquinoline and indole alkaloids|first1=Enrique L.|last1=Larghi|first2=Marcela|last2=Amongero|first3=Andrea B. J.|last3=Bracca|first4=Teodoro S.|last4=Kaufman|journal=Arkivoc|volume=RL-1554K|pages=98–153|date=2005|issue=12|doi=10.3998/ark.5550190.0006.c09|doi-access=free|hdl=2027/spo.5550190.0006.c09|hdl-access=free}}{{cite book|first1=Teodoro S.|last1=Kaufman|chapter=Synthesis of Optically-Active Isoquinoline and Indole Alkaloids Employing the Pictet–Spengler Condensation with Removable Chiral Auxiliaries Bound to Nitrogen|title=New Methods for the Asymmetric Synthesis of Nitrogen Heterocycles|editor-first=J. L.|editor-last=Vicario|isbn=978-81-7736-278-7|publisher=Research SignPost|location=Thiruvananthapuram|date=2005|pages=99–147}} One example is the Pictet-Spengler reaction between tryptophan derivatives and aldehydes,{{cite journal |last1=Bonnet |first1=D. |last2=Ganesan |first2=A. | journal = J. Comb. Chem. | year = 2002 | volume = 4 | issue = 6 | pages = 546–548 | title = Solid-Phase Synthesis of Tetrahydro-β-carbolinehydantoins via the N-Acyliminium Pictet–Spengler Reaction and Cyclative Cleavage | doi = 10.1021/cc020026h |pmid=12425597 }} which produces a mixture of diastereomers, leading to reduced yield of the desired product.

Indoles are susceptible to hydrogenation of the imine subunitZhu, G.; Zhang, X. Tetrahedron: Asymmetry 1998, 9, 2415. to give indolines.

File:ImineScope3.png

• Indole-3-butyric acid
• Indole test
• Isoindole
• Isoindoline
• Skatole (3-methylindole)

{{reflist|30em}}

• {{cite book|title=Indoles Part One|editor-first=W. J.|editor-last=Houlihan|publisher=Wiley Interscience|location=New York|date=1972}}{{ISBN missing}}
• {{cite book|first=R. J.|last=Sundberg|year=1996|title=Indoles|publisher=Academic Press|location=San Diego|isbn=978-0-12-676945-6}}
• {{cite book|first=J. A.|last=Joule|author2=Mills, K.|year=2000|title=Heterocyclic Chemistry|publisher=Blackwell Science|location=Oxford, UK|isbn=978-0-632-05453-4}}
• {{cite book|last=Joule|first=J.|title=Science of Synthesis|editor-first=Thomas|editor-last=E. J.|publisher=Thieme|location=Stuttgart|date=2000|volume=10|page=361|isbn=978-3-13-112241-4}}
• {{Cite journal|last1=Schoenherr|first1=H.|last2=Leighton|first2=J. L.|title=Direct and Highly Enantioselective Iso-Pictet-Spengler Reactions with α-Ketoamides: Access to Underexplored Indole Core Structures|journal=Org. Lett.|date=2012|volume=14|issue=10|pages=2610–3|doi=10.1021/ol300922b|pmid=22540677}}

{{Commons category|1H-Indole}}

• [https://www.organic-chemistry.org/synthesis/heterocycles/benzo-fused/indoles.shtm Synthesis of indoles (overview of recent methods)]
• [http://www.chemsynthesis.com/ring-fused/indoles/page-1.html Synthesis and properties of indoles] at chemsynthesis.com

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