2C-5-TOET

2C-5-TOET
Clinical data
Other names	5-Thio-2C-E; 5T-2C-E; 4-Ethyl-2-methoxy-5-methylthiophenethylamine; 2-Methoxy-4-ethyl-5-methylthiophenethylamine
ATC code	None;
Identifiers
	IUPAC name 2-(4-ethyl-2-methoxy-5-methylsulfanylphenyl)ethanamine;
PubChem CID	15915366;
ChemSpider	45598234;
Chemical and physical data
Formula	C12H19NOS
Molar mass	225.35 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCC1=CC(=C(C=C1SC)CCN)OC;
	InChI InChI=1S/C12H19NOS/c1-4-9-7-11(14-2)10(5-6-13)8-12(9)15-3/h7-8H,4-6,13H2,1-3H3; Key:NMFLGCDBOWGERA-UHFFFAOYSA-N;

2C-5-TOET, also known as 2-methoxy-4-ethyl-5-methylthiophenethylamine or as 5-thio-2C-E, is a chemical compound and possible psychedelic drug of the phenethylamine and thio-2C families related to the psychedelics 2C-E and 5-TOET (5-thio-DOET).^[1]^[2]^[3]^[4] It is the analogue of 2C-E in which the methoxy group at the 5 position has been replaced with a methylthio group.^[1]^[2]^[4] In addition, the compound is the phenethylamine (i.e., α-desmethyl) analogue of 5-TOET (the 5-methylthio analogue of DOET).^[1]^[2]^[3]^[4]

2C-5-TOET was first described in the scientific literature by Alexander Shulgin and Peyton Jacob III in 1983.^[4] Subsequently, it was also described by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).^[1]^[2]^[3] However, he only synthesized the compound and did not test it.^[1]^[2]^[3]^[4] As such, its properties and effects are unknown.^[1]^[2]^[3]^[4] The related drug 5-TOET is known to be robustly active as a psychedelic but to be about 5-fold less potent than DOET.^[1]^[5] The chemical synthesis of 2C-5-TOET has been described.^[1]^[4] Other related compounds include 2C-2-TOM (2-thio-DOM), 2C-5-TOM (5-thio-DOM), and 2C-2-TOET (2-thio-DOET).^[1]^[2]^[3]^[4]

2C-5-TOET and/or precursors or intermediates have reportedly been encountered as novel designer drugs.^[6]^[7]^[8] Similarly, 2C-2-TOM and 2C-2-TOET have reportedly been encountered as designer drugs.^[9] Thio-2Cs like 2C-5-TOET are not controlled substances in Canada as of 2025.^[10]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. "#170 5-TOET". As with the other members of the TOM's and TOET's, the phenethylamine homologue of 5-TOET was synthesized, but had never been started in human evaluation. The aldehyde from above, 4-ethyl-2-methoxy-5-(methylthio)benzaldehyde, was condensed with nitroethane (as reagent and as solvent) and with ammonium acetate as catalyst to give the nitrostyrene as spectacular canary-yellow electrostatic crystals with a mp of 91-92 °C. Anal. (C12H15NO3S) C,H. This was reduced with aluminum hydride (from cold THF-dissolved lithium aluminum hydride and 100% sulfuric acid) to the phenethylamine 4-ethyl-2-methoxy-5-methylthiophenethylamine (2C-5-TOET) which, when totally freed from water of hydration by drying at 100 °C under a hard vacuum, had a mp of 216-217 °C. Anal. (C12H20ClNOS) C,H.
^ ^a ^b ^c ^d ^e ^f ^g Shulgin A, Manning T, Daley P (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. p. 108. ISBN 978-0-9630096-3-0.
^ ^a ^b ^c ^d ^e ^f Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. pp. 823–824. ISBN 978-3-03788-700-4. OCLC 858805226. Archived from the original on 21 August 2025.
^ ^a ^b ^c ^d ^e ^f ^g ^h Jacob P, Shulgin AT (May 1983). "Sulfur analogues of psychotomimetic agents. 2. Analogues of (2,5-dimethoxy-4-methylphenyl)-and (2,5-dimethoxy-4-ethylphenyl)isopropylamine". Journal of Medicinal Chemistry. 26 (5): 746–752. doi:10.1021/jm00359a021. PMID 6842515.
^ Nichols DE (1994). "Medicinal Chemistry and Structure-Activity Relationships". In Cho AK, Segal DS (eds.). Amphetamine and Its Analogs: Psychopharmacology, Toxicology, and Abuse. Academic Press. pp. 3–41. ISBN 978-0-12-173375-9. Biological activity is low in compounds in which the oxygen atom of either the 2- or the 5-methoxy group has been replaced with a sulfur, illustrating the difficulty in developing bioisosteres of the 2,5-dimethoxy-substituted aromatic nucleus. However, if relative importance were assigned to the two methoxy groups, the 2-methoxy group would appear to be more, critical for optimal activity (Jacob et al., 1977). For example, referring to Table l, when the 2-methoxy group of DOEt is replaced with a methylthio group, in vivo activity is reduced by more than one order of magnitude (Jacob and Shulgin, 1983; Shulgin and Shulgin, 1991). However, the replacement of the 5-methoxy oxygen with a sulfur reduces activity only 4- to 6-fold. Similarly, when the 2-methoxy group of DOM is replaced with a methylthio group, activity drops by a factor of 10–20, whereas similar replacement of the 5-methoxy only reduces activity 5- to 10-fold (Jacob et al., 1977; Shulgin and Shulgin, 1991).
^ Yurchenko R, Zayats M, Piatsetskaya A, Yurchenko V (September 2025). New psychoactive substances in the Volga Federal District. Scientific and practical conference with international participation "Chemical and toxicological studies in the Volga Federal District". p. 41. doi:10.13140/RG.2.2.12993.42088. Ufa, KDL GBUZ RKND MZ RB] (presentation of the report in Russian). Retrieved 21 January 2026. [...] 2C-5-TOET PROP. 5-TOET TFA. [...]
^ "2C-5-TOET". spectrabase.com. 2C-5-TOET. Compound with spectra: 3 MS (GC) [...] SpectraBase Compound ID: 9tCCQhZhq99 [...] This compound is available in the following databases: Mass Spectra of Designer Drugs 2025. Author: Peter Rösner [...]
^ "Designer Drugs 2023 :: 2C-5-TOET AC". Chemograph Plus. Retrieved 21 January 2026.
^ Catalani V, Corkery JM, Guirguis A, Napoletano F, Arillotta D, Zangani C, et al. (August 2021). "Psychonauts' psychedelics: A systematic, multilingual, web-crawling exercise". European Neuropsychopharmacology. 49: 69–92. doi:10.1016/j.euroneuro.2021.03.006. PMID 33857740. Table 1 NPSfinder® psychedelic phenethylamines and comparisons with EMCDDA and UNODC databases. [...] 11 2C-2-TOET [...] 12 2C-2-TOM [...]
^ "Controlled Drugs and Substances Act". Department of Justice Canada. 5 December 2025. Retrieved 20 January 2026.

External links

2C-5-TOET - Isomer Design

[PiHKAL-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. "#170 5-TOET". As with the other members of the TOM's and TOET's, the phenethylamine homologue of 5-TOET was synthesized, but had never been started in human evaluation. The aldehyde from above, 4-ethyl-2-methoxy-5-(methylthio)benzaldehyde, was condensed with nitroethane (as reagent and as solvent) and with ammonium acetate as catalyst to give the nitrostyrene as spectacular canary-yellow electrostatic crystals with a mp of 91-92 °C. Anal. (C12H15NO3S) C,H. This was reduced with aluminum hydride (from cold THF-dissolved lithium aluminum hydride and 100% sulfuric acid) to the phenethylamine 4-ethyl-2-methoxy-5-methylthiophenethylamine (2C-5-TOET) which, when totally freed from water of hydration by drying at 100 °C under a hard vacuum, had a mp of 216-217 °C. Anal. (C12H20ClNOS) C,H.

[Shulgin_2011-2] ^ ^a ^b ^c ^d ^e ^f ^g Shulgin A, Manning T, Daley P (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. p. 108. ISBN 978-0-9630096-3-0.

[Trachsel_2013-3] ^ ^a ^b ^c ^d ^e ^f Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. pp. 823–824. ISBN 978-3-03788-700-4. OCLC 858805226. Archived from the original on 21 August 2025.

[Jacob_1983-4] ^ ^a ^b ^c ^d ^e ^f ^g ^h Jacob P, Shulgin AT (May 1983). "Sulfur analogues of psychotomimetic agents. 2. Analogues of (2,5-dimethoxy-4-methylphenyl)-and (2,5-dimethoxy-4-ethylphenyl)isopropylamine". Journal of Medicinal Chemistry. 26 (5): 746–752. doi:10.1021/jm00359a021. PMID 6842515.

[Nichols_1994-5] Nichols DE (1994). "Medicinal Chemistry and Structure-Activity Relationships". In Cho AK, Segal DS (eds.). Amphetamine and Its Analogs: Psychopharmacology, Toxicology, and Abuse. Academic Press. pp. 3–41. ISBN 978-0-12-173375-9. Biological activity is low in compounds in which the oxygen atom of either the 2- or the 5-methoxy group has been replaced with a sulfur, illustrating the difficulty in developing bioisosteres of the 2,5-dimethoxy-substituted aromatic nucleus. However, if relative importance were assigned to the two methoxy groups, the 2-methoxy group would appear to be more, critical for optimal activity (Jacob et al., 1977). For example, referring to Table l, when the 2-methoxy group of DOEt is replaced with a methylthio group, in vivo activity is reduced by more than one order of magnitude (Jacob and Shulgin, 1983; Shulgin and Shulgin, 1991). However, the replacement of the 5-methoxy oxygen with a sulfur reduces activity only 4- to 6-fold. Similarly, when the 2-methoxy group of DOM is replaced with a methylthio group, activity drops by a factor of 10–20, whereas similar replacement of the 5-methoxy only reduces activity 5- to 10-fold (Jacob et al., 1977; Shulgin and Shulgin, 1991).

[Yurchenko_2025-6] Yurchenko R, Zayats M, Piatsetskaya A, Yurchenko V (September 2025). New psychoactive substances in the Volga Federal District. Scientific and practical conference with international participation "Chemical and toxicological studies in the Volga Federal District". p. 41. doi:10.13140/RG.2.2.12993.42088. Ufa, KDL GBUZ RKND MZ RB] (presentation of the report in Russian). Retrieved 21 January 2026. [...] 2C-5-TOET PROP. 5-TOET TFA. [...]

[SpectraBase-7] "2C-5-TOET". spectrabase.com. 2C-5-TOET. Compound with spectra: 3 MS (GC) [...] SpectraBase Compound ID: 9tCCQhZhq99 [...] This compound is available in the following databases: Mass Spectra of Designer Drugs 2025. Author: Peter Rösner [...]

[ChemographPlus-8] "Designer Drugs 2023 :: 2C-5-TOET AC". Chemograph Plus. Retrieved 21 January 2026.

[Catalani_2021-9] Catalani V, Corkery JM, Guirguis A, Napoletano F, Arillotta D, Zangani C, et al. (August 2021). "Psychonauts' psychedelics: A systematic, multilingual, web-crawling exercise". European Neuropsychopharmacology. 49: 69–92. doi:10.1016/j.euroneuro.2021.03.006. PMID 33857740. Table 1 NPSfinder® psychedelic phenethylamines and comparisons with EMCDDA and UNODC databases. [...] 11 2C-2-TOET [...] 12 2C-2-TOM [...]

[CDSA2025-10] "Controlled Drugs and Substances Act". Department of Justice Canada. 5 December 2025. Retrieved 20 January 2026.

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See also

References

External links