{ "id": "epkprnte5d", "slug": "pictet-spengler-reaction", "title": "Pictet–Spengler reaction", "updated": "2026-10-15", "topic_path": [ { "id": "physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/topics/physical" }, { "id": "physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry" }, { "id": "physical.chemistry.methods", "label": "Chemical principles and methods", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods" }, { "id": "physical.chemistry.methods.chemical-synthesis", "label": "Chemical synthesis", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis" }, { "id": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis.named-preparative-methods" }, { "id": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-ho-to-z", "label": "Titles Ho to Z", "api_url": "https://www.edgepedia.org/api/v1/topics/physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-ho-to-z" } ], "geo": [ { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Non-geographic · 1800 to 1945: Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.t1800", "label": "Non-geographic · 1800 to 1945", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800" }, { "id": "geo.nongeo.t1800.physical", "label": "Physical world and mathematics", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical" }, { "id": "geo.nongeo.t1800.physical.chemistry", "label": "Chemistry", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods", "label": "Chemical principles and methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis", "label": "Chemical synthesis", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis" }, { "id": "geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods", "label": "Named synthetic methods", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.t1800.physical.chemistry.methods.chemical-synthesis.named-preparative-methods" } ] } ], "excerpt": "The Pictet–Spengler reaction is an acid-promoted cyclocondensation in which a β-arylethylamine and an aldehyde or ketone form tetrahydroisoquinolines and tetrahydro-β-carbolines, key alkaloid scaffolds; reported by Pictet and Spengler in 1911.", "snippet": "The Pictet–Spengler reaction is an acid-promoted cyclocondensation in which a β-arylethylamine and an aldehyde or ketone form tetrahydroisoquinolines and tetrahydro-β-carbolines, key alkaloid scaffolds; reported by Pictet and Spengler in 1911.", "node": "physical.chemistry.methods.chemical-synthesis.named-preparative-methods.alpha-ho-to-z", "markdown": "# Pictet–Spengler reaction\n\nThe Pictet–Spengler reaction is an acid-promoted cyclocondensation in which a β-arylethylamine, such as phenethylamine or tryptamine, condenses with an aldehyde or ketone, and the resulting iminium ion is trapped intramolecularly by an electron-rich aromatic ring to give tetrahydroisoquinolines, tetrahydro-β-carbolines, and related heterocycles. It is regarded as a special type of [Mannich reaction](https://www.edgepedia.org/mannich-reaction) and as a principal method for building alkaloid scaffolds, with efficient enzymatic and non-enzymatic versions available today.[1](https://onlinelibrary.wiley.com/doi/10.1002/anie.201008071) Some reactive substrates give acceptable yields even under physiological conditions.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6017108/)\n\n| Key fact | Detail |\n|---|---|\n| Products | 1,2,3,4-Tetrahydroisoquinolines from phenethylamines; tetrahydro-β-carbolines from tryptamines[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6017108/) |\n| Starting materials | β-Arylethylamine + aldehyde or ketone, acid catalyst[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC6017108/) |\n| Discovery | Amé Pictet and Theod. Spengler, 1911, phenethylamine + methylal in hydrochloric acid[3](https://doi.org/10.1002/cber.19110440309) |\n| Common catalysts | Trifluoroacetic acid (TFA), p-toluenesulfonic acid (PTSA), BF₃·Et₂O[4](https://www.sciencedirect.com/science/article/abs/pii/S0065272518300308) |\n| Biosynthetic role | Strictosidine synthase makes strictosidine, precursor to over 2,000 monoterpenoid indole alkaloids[5](https://www.sciencedirect.com/science/article/abs/pii/S1367593119301474) |\n| Asymmetric catalysis | Chiral Brønsted acids, thioureas, SPINOL phosphoric acids, IDPi catalysts; up to 97:3 er reported for 1-aryl THIQs[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC11487569/) |\n| Biocatalysis | Norcoclaurine synthase, strictosidine synthase, McbB, KslB, and engineered variants[5](https://www.sciencedirect.com/science/article/abs/pii/S1367593119301474) |\n\n## How it works\n\nThe reaction proceeds through a defined sequence. The amine and carbonyl compound first condense to an aminol (hemiaminal), which dehydrates to an iminium ion; the electron-rich aromatic ring then attacks the iminium carbon in an intramolecular electrophilic aromatic substitution, and deprotonation restores aromaticity and closes the ring, generating a stereogenic center at C1.[5](https://www.sciencedirect.com/science/article/abs/pii/S1367593119301474) In a detailed study of an N-carbamoyl homoveratrylamine system, Brønsted acid-mediated attack on the protonated aldehyde gives the hemiaminal, dehydration forms an N-acyliminium ion, arene attack gives an arenium ion, and deprotonation regenerates the catalyst.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC11487569/)\n\nWhich step is slow depends on the substrate. For the enzyme strictosidine synthase, kinetic isotope effects and pH dependence indicated iminium formation is acid-catalyzed and final deprotonation is base-catalyzed, and ab initio calculations indicated no spiroindolenine intermediate.[5](https://www.sciencedirect.com/science/article/abs/pii/S1367593119301474)\n\n## How it is done\n\nIn the original 1911 procedure, phenethylamine and formaldehyde dimethyl acetal (methylal) were cyclized in the presence of hydrochloric acid to give 1,2,3,4-tetrahydroisoquinoline.[3](https://doi.org/10.1002/cber.19110440309) Today the iminium cyclization is most commonly catalyzed by strong Brønsted acids, with TFA and p-toluenesulfonic acid widely used; acetic acid, sulfuric acid, hydrochloric acid, Lewis acids, iodine, and AuCl₃/AgOTf are also employed.[7](https://researchonline.ljmu.ac.uk/id/eprint/23111/1/chapter_1.pdf) BF₃·Et₂O is likewise popular, and heterogeneous acids such as nanosilica sulfuric acid and montmorillonite clay have been reported.[4](https://www.sciencedirect.com/science/article/abs/pii/S0065272518300308)\n\n## Origin\n\nThe reaction was reported by [Amé Pictet](https://www.edgepedia.org/ame-pictet) and Theod. Spengler in 1911, in the paper \"Über die Bildung von Isochinolin-derivaten durch Einwirkung von Methylal auf Phenyl-äthylamin, Phenyl-alanin und Tyrosin\" in Berichte der deutschen chemischen Gesellschaft, volume 44, pages 2030–2036; the authors were at the Organisches Laboratorium der Universität, Genf, and the manuscript was received on 20 June 1911.[3](https://doi.org/10.1002/cber.19110440309) The same authors published a parallel French-language paper, \"Sur un nouveau mode de formation des bases isoquinoliques tétrahydrogénées\", in Archives des sciences physiques et naturelles in October 1911.[8](https://archive-ouverte.unige.ch/unige:190224) In the same year, Pictet and Alfons Gams reported the related synthesis of oxyberberine.[9](https://doi.org/10.1002/cber.19110440310) A centenary review by Joachim Stöckigt, Andrey P. Antonchick, Fangrui Wu, and [Herbert Waldmann](https://www.edgepedia.org/herbert-waldmann) describes the condensation of aryl ethylamines and aldehydes as the most important method for the synthesis of alkaloid scaffolds.[1](https://onlinelibrary.wiley.com/doi/10.1002/anie.201008071) Eric D. Cox and James M. Cook reviewed the condensation in Chemical Reviews in 1995.[10](https://doi.org/10.1021/cr00038a004)\n\n## Variants\n\n**Asymmetric catalysis.** A catalytic asymmetric Pictet–Spengler reaction using a chiral Brønsted acid was reported by Jayasree Seayad, Abdul Majeed Seayad, and [Benjamin List](https://www.edgepedia.org/benjamin-list) in 2006.[11](https://doi.org/10.1021/ja057444l) Related catalytic enantioselective approaches include acyl-Pictet–Spengler reactions by Mark S. Taylor and [Eric N. Jacobsen](https://www.edgepedia.org/eric-n-jacobsen) (2004),[12](https://doi.org/10.1021/ja046259p) sulfenyliminium-ion chemistry by Martin J. Wanner and colleagues (2007),[13](https://doi.org/10.1002/anie.200701808) hydroxylactam cyclizations with H-bond donor anion-binding catalysis by Izzat T. Raheem and colleagues (2007),[14](https://doi.org/10.1021/ja076179w) thiourea-catalyzed iso-Pictet–Spengler reactions by Yunmi Lee, Rebekka S. Klausen, and Eric N. Jacobsen (2011),[15](https://doi.org/10.1021/ol202300t) SPINOL-phosphoric acid catalysis by Dan Huang and colleagues (2012),[16](https://doi.org/10.1002/chem.201103207) conjugate-base-stabilized Brønsted acids for unmodified tryptamine by Nisha Mittal, Diana X. Sun, and [Daniel Seidel](https://www.edgepedia.org/daniel-seidel) (2014),[17](https://doi.org/10.1021/ol403773a) and chiral imidazoline-phosphoric acid catalysts for acyclic α-ketoesters by Shuichi Nakamura and colleagues (2022).[18](https://doi.org/10.1021/acs.orglett.1c04316) Substrate-controlled versions use N-sulfinyl tryptamines to give enantiopure tetrahydro-β-carbolines.[19](https://doi.org/10.1021/ol006034t) Organic Reactions volume 114 (2024) surveys enantioselective Pictet–Spengler reactions promoted by chiral Brønsted acids, Lewis acids, and hydrogen-bond donors such as thioureas, with literature coverage to December 2019.[20](https://www.organicreactions.org/pubchapter/enantioselective-pictet-spengler-reactions/) In 2025, Shigenobu Umemiya, Shinnosuke Nara, and Masahiro Terada reported a chiral phosphoric acid-catalyzed enantioselective Pictet–Spengler reaction of tryptamines with trifluoromethyl alkynyl ketones, giving CF₃-substituted tetrahydro-β-carbolines.[21](https://doi.org/10.1021/acs.orglett.5c01864)\n\n**Metal and superacid catalysis.** So Won Youn developed a Pictet–Spengler reaction catalyzed by AuCl₃/AgOTf in 2006,[22](https://doi.org/10.1021/jo0524775) and Akihiro Yokoyama, Tomohiko Ohwada, and Koichi Shudo studied prototype reactions catalyzed by [superacids](https://www.edgepedia.org/superacid), involving dicationic superelectrophiles, in 1998.[23](https://doi.org/10.1021/jo982019e)\n\n**Oxa-Pictet–Spengler.** The oxa-Pictet–Spengler cyclization, reviewed by Teodoro S. Kaufman and Enrique L. Larghi in 2006, uses an oxygen nucleophile to build isochromans and related pyran-type heterocycles.[24](https://doi.org/10.1055/s-2005-918502)\n\n**Biocatalysis.** Pictet–Spenglerases catalyze the reaction in alkaloid biosynthesis: strictosidine synthase (STR) joins tryptamine and secologanin,[5](https://www.sciencedirect.com/science/article/abs/pii/S1367593119301474) norcoclaurine synthase (NCS) joins dopamine and 4-hydroxyphenylacetaldehyde in a \"dopamine first\" binding mechanism,[5](https://www.sciencedirect.com/science/article/abs/pii/S1367593119301474) and TfNCS accepts unactivated ketones, enabling 1,1′-disubstituted and spiro-tetrahydroisoquinolines with no equivalent stereoselective chemical methods.[25](https://www.nature.com/articles/ncomms14883) Structural and mechanistic work on KslB, a bacterial Pictet–Spenglerase from Kitasatospora setae that condenses L-tryptophan with α-ketoglutarate in kitasetaline biosynthesis, showed only 9% sequence identity to McbB and 2% to strictosidine synthase; docking supports indole attack on the C2′ iminium carbon from its si face, with Glu274 as general base.[26](https://pubs.rsc.org/en/content/articlehtml/2025/cb/d5cb00070j)\n\n## Applications\n\nThe reaction is a staple of alkaloid total synthesis. Jin Li, Tao Wang, Peng Yu, and colleagues used an asymmetric Pictet–Spengler reaction in an enantiospecific route to (+)-ajmaline, alkaloid G, and norsuaveoline (1999); in a PSR/Dieckmann sequence, (+)-ajmaline and alkaloid G were obtained in 93% and 92% yield, and norsuaveoline was completed in 10 vessels with 28% overall yield.[27](https://doi.org/10.1021/ja990184l) Many strategies to the eudistomins rest on the reaction,[4](https://www.sciencedirect.com/science/article/abs/pii/S0065272518300308) and Pictet–Spengler products serve as key intermediates toward yohimbine, [mitragynine](https://www.edgepedia.org/mitragynine), harmicine, and crispine A, among others.[20](https://www.organicreactions.org/pubchapter/enantioselective-pictet-spengler-reactions/) In biosynthesis, the strictosidine pathway supplies over 2,000 monoterpenoid indole alkaloids with activities including antimalarial (quinine), antitumor (camptothecin), and antiarrhythmic (ajmaline).[5](https://www.sciencedirect.com/science/article/abs/pii/S1367593119301474) A one-pot cascade couples whole-cell alcohol oxidation ([Gluconobacter oxydans](https://www.edgepedia.org/gluconobacter-oxydans) or Komagataella pastoris) with a potassium-phosphate-catalyzed aqueous [annulation](https://www.edgepedia.org/annulation), converting tyramine and C2–C5 alcohols to tetrahydroisoquinolines in >90% isolated yield and tryptamines to tryptolines in >40% yield.[28](https://par.nsf.gov/servlets/purl/10493255)\n\n## Limitations and alternatives\n\nThe Pictet–Spengler and Bischler–Napieralski reactions are the most widely employed methods for preparing β-carbolines, but both deliver tetrahydro- or dihydro-β-carbolines, and in most cases an additional aromatization step is required to reach fully aromatic β-carbolines; one-pot and cascade methods have been developed in which the Pictet–Spengler cyclization forms the β-carboline directly, avoiding a separate oxidation.[7](https://researchonline.ljmu.ac.uk/id/eprint/23111/1/chapter_1.pdf) The Bischler–Napieralski cyclization commonly requires harsh conditions, using POCl₃ as dehydrating agent with high-boiling solvents such as xylene or toluene at reflux; milder variants use T3P (1.5 equiv, eliminating one equivalent of water per equivalent of cyclized amide) or (PhO)₃P·Cl₂ at −30 °C in dichloromethane with triethylamine.[7](https://researchonline.ljmu.ac.uk/id/eprint/23111/1/chapter_1.pdf) Substrate electronics also limit the asymmetric variants: in a chiral phosphoric acid route to CF₃-substituted tetrahydro-β-carbolines, electron-deficient (CF₃-substituted) tryptamines gave low yields, and a 4-bromo tryptamine reacted very slowly, giving only 18% yield, though with excellent enantioselectivity.[21](https://doi.org/10.1021/acs.orglett.5c01864)\n\n## References\n\n1. [The Pictet–Spengler Reaction in Nature and in Organic Chemistry (Stöckigt, Antonchick, Wu, Waldmann)](https://onlinelibrary.wiley.com/doi/10.1002/anie.201008071)\n2. [Application of the Asymmetric Pictet–Spengler Reaction in the Total Synthesis of Natural Products and Relevant Biologically Active Compounds](https://pmc.ncbi.nlm.nih.gov/articles/PMC6017108/)\n3. [Amé Pictet, Theod. Spengler (1911). Über die Bildung von Isochinolin‐derivaten durch Einwirkung von Methylal auf Phenyl‐äthylamin, Phenyl‐alanin und Tyrosin. Berichte der deutschen chemischen Gesellschaft.](https://doi.org/10.1002/cber.19110440309)\n4. [The Pictet–Spengler Reaction: A Powerful Strategy for the Synthesis of Heterocycles (Advances in Heterocyclic Chemistry, Chapter Three)](https://www.sciencedirect.com/science/article/abs/pii/S0065272518300308)\n5. [Pictet–Spenglerases in alkaloid biosynthesis: Future applications in biocatalysis (Current Opinion in Biotechnology; repository copy merged)](https://www.sciencedirect.com/science/article/abs/pii/S1367593119301474)\n6. [Highly Acidic Electron-Rich Brønsted Acids Accelerate Asymmetric Pictet–Spengler Reactions by Virtue of Stabilizing Cation–π Interactions (JACS, 2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC11487569/)\n7. [Methodologies for the Synthesis of β-Carbolines (Boswood & Roesner, Targets in Heterocyclic Systems, 2024, DOI 10.17374/targets.2024.27.1)](https://researchonline.ljmu.ac.uk/id/eprint/23111/1/chapter_1.pdf)\n8. [Sur un nouveau mode de formation des bases isoquinoliques tétrahydrogénées](https://archive-ouverte.unige.ch/unige:190224)\n9. [Amé Pictet, Alfons Gams (1911). Synthese des Oxy‐berberins. Berichte der deutschen chemischen Gesellschaft.](https://doi.org/10.1002/cber.19110440310)\n10. [Eric D. Cox, James M. Cook (1995). The Pictet-Spengler condensation: a new direction for an old reaction. Chemical Reviews.](https://doi.org/10.1021/cr00038a004)\n11. [Jayasree Seayad, Abdul Majeed Seayad, Benjamin List (2006). Catalytic Asymmetric Pictet−Spengler Reaction. Journal of the American Chemical Society.](https://doi.org/10.1021/ja057444l)\n12. [Mark S. Taylor, Eric N. Jacobsen (2004). Highly Enantioselective Catalytic Acyl-Pictet−Spengler Reactions. Journal of the American Chemical Society.](https://doi.org/10.1021/ja046259p)\n13. [Martin J. Wanner and colleagues (2007). Catalytic Asymmetric Pictet–Spengler Reactions via Sulfenyliminium Ions. Angewandte Chemie International Edition.](https://doi.org/10.1002/anie.200701808)\n14. [Izzat T. Raheem and colleagues (2007). Enantioselective Pictet−Spengler-Type Cyclizations of Hydroxylactams: H-Bond Donor Catalysis by Anion Binding. Journal of the American Chemical Society.](https://doi.org/10.1021/ja076179w)\n15. [Yunmi Lee, Rebekka S. Klausen, Eric N. Jacobsen (2011). Thiourea-Catalyzed Enantioselective Iso-Pictet–Spengler Reactions. Organic Letters.](https://doi.org/10.1021/ol202300t)\n16. [Dan Huang and colleagues (2012). Highly Enantioselective Pictet–Spengler Reaction Catalyzed by SPINOL‐Phosphoric Acids. Chemistry - A European Journal.](https://doi.org/10.1002/chem.201103207)\n17. [Nisha Mittal, Diana X. Sun, Daniel Seidel (2014). Conjugate-Base-Stabilized Brønsted Acids: Catalytic Enantioselective Pictet–Spengler Reactions with Unmodified Tryptamine. Organic Letters.](https://doi.org/10.1021/ol403773a)\n18. [Shuichi Nakamura and colleagues (2022). Enantioselective Pictet–Spengler Reaction of Acyclic α-Ketoesters Using Chiral Imidazoline-Phosphoric Acid Catalysts. Organic Letters.](https://doi.org/10.1021/acs.orglett.1c04316)\n19. [Christiaan Gremmen and colleagues (2000). Enantiopure Tetrahydro-β-carbolines via Pictet−Spengler Reactions with N-Sulfinyl Tryptamines. Organic Letters.](https://doi.org/10.1021/ol006034t)\n20. [Enantioselective Pictet-Spengler Reactions (Organic Reactions, Vol. 114, Seidel, 2024)](https://www.organicreactions.org/pubchapter/enantioselective-pictet-spengler-reactions/)\n21. [Shigenobu Umemiya, Shinnosuke Nara, Masahiro Terada (2025). Chiral Phosphoric Acid-Catalyzed Enantioselective Pictet–Spengler Reaction for Concise Synthesis of CF3-Substituted Tetrahydro-β-Carbolines. Organic Letters.](https://doi.org/10.1021/acs.orglett.5c01864)\n22. [So Won Youn (2006). Development of the Pictet−Spengler Reaction Catalyzed by AuCl3/AgOTf. The Journal of Organic Chemistry.](https://doi.org/10.1021/jo0524775)\n23. [Akihiro Yokoyama, Tomohiko Ohwada, Koichi Shudo (1998). Prototype Pictet−Spengler Reactions Catalyzed by Superacids. Involvement of Dicationic Superelectrophiles. The Journal of Organic Chemistry.](https://doi.org/10.1021/jo982019e)\n24. [Teodoro S. Kaufman, Enrique L. Larghi (2006). The Oxa-Pictet-Spengler Cyclization: Synthesis of Isochromans and Related Pyran-Type Heterocycles. Synthesis.](https://doi.org/10.1055/s-2005-918502)\n25. [Enzyme catalysed Pictet-Spengler formation of chiral 1,1'-disubstituted- and spiro-tetrahydroisoquinolines (Nature Communications, 2017)](https://www.nature.com/articles/ncomms14883)\n26. [Structural and mechanistic insights into KslB, a bacterial Pictet–Spenglerase in kitasetaline biosynthesis (RSC Chemical Biology, 2025)](https://pubs.rsc.org/en/content/articlehtml/2025/cb/d5cb00070j)\n27. [Jin Li and colleagues (1999). General Approach for the Synthesis of Ajmaline/Sarpagine Indole Alkaloids: Enantiospecific Total Synthesis of (+)-Ajmaline, Alkaloid G, and Norsuaveoline via the Asymmetric Pictet−Spengler Reaction. Journal of the American Chemical Society.](https://doi.org/10.1021/ja990184l)\n28. [Interfacing Whole Cell Biocatalysis with a Biocompatible Pictet-Spengler Reaction for One-Pot Syntheses of Tetrahydroisoquinolines and Tryptolines](https://par.nsf.gov/servlets/purl/10493255)\n\n---\n*Topic: Encyclopedia › Physical world and mathematics › Chemistry › Chemical principles and methods › Chemical synthesis › Named synthetic methods › Titles Ho to Z*\n\n*Initially written Sep 29, 2026 · Edited: Oct 15, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/pictet-spengler-reaction", "markdown_url": "https://www.edgepedia.org/pictet-spengler-reaction.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Pictet–Spengler reaction\", Edgepedia (EdgeChat), https://www.edgepedia.org/pictet-spengler-reaction. Edgepedia Community License 1.0.", "credit_md": "\"[Pictet–Spengler reaction](https://www.edgepedia.org/pictet-spengler-reaction)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/pictet-spengler-reaction](https://www.edgepedia.org/pictet-spengler-reaction). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Pictet–Spengler reaction\", Edgepedia (EdgeChat), https://www.edgepedia.org/pictet-spengler-reaction. Edgepedia Community License 1.0.", "speakable": "The Pictet–Spengler reaction is an acid-promoted cyclocondensation in which a β-arylethylamine and an aldehyde or ketone form tetrahydroisoquinolines and tetrahydro-β-carbolines, key alkaloid scaffolds; reported by Pictet and Spengler in 1911." }