The Vespiary

Synthesis of Novel (Phenylalkyl)amines for Structure-Activity Relationship Investigation. Part 1. Mescaline Derivatives

Abstract

The synthesis and the spectroscopic data of 14 novel 4-substituted mescaline derivatives are reported. Starting from syringaldehyde (= 4-hydroxy-3,5-dimethoxybenzaldehyde), several ethers were obtained from reaction witha series of corresponding saturated and unsaturated alkyl- and fluoroalkyl halides. Henry-reaction with MeNO₂ or EtNO₂ followed to afford the nitroalkenes, which were then reduced with AlH₃ to the desired phenethylamine and amphetamine derivatives.

Helv. Chim. Acta. 2002, 85(9), 3019-3026 (https://www.thevespiary.org/rhodium/Rhodium/pdf/mescaline.4-subst.analogs.pdf)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/mescaline.4-subst.analogs.pdf) (In German)

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Let's keep an eye open for any further articles by this author, Daniel Trachsel. He seems to have published a book too,

Psychedelische Chemie (http://www.amazon.de/exec/obidos/ASIN/390708053X/)

(http://www.amazon.de/exec/obidos/ASIN/390708053X/)

The book seems to be available from the publisher's website:

http://www.nachtschatten.ch/prod/buch_231.htm (http://www.nachtschatten.ch/prod/buch_231.htm)

This book seems to be very very interesting..
It seems to be like other well-known books here at this place...

From amazon translated: "So that also the curious chemist can satisfy his thirst for knowledge, detailed synthesis instructions inclusive reaction schemes and alternative syntheses with literature data are included. Based on some examples also novel synthesis reactions are presented."

(Damit auch der neugierige Chemiker seinen Wissensdurst stillen kann, liegen zudem detaillierte Synthesevorschriften inklusive Reaktionsschemen und Alternativsynthesen mit Literaturangaben vor. Anhand einiger Beispiele werden auch neuartigere Synthesereaktionen präsentiert.)

Translated from nachtschatten page: "For the approx. 50 mind-altering substances comprehensive and clearly arranged synthesis instructions and alternative synthesis stragegies with literature data are presented." (ml: The sense is not really clear. It could be, that the synthesis instructions are additional included to the whole other information in their book about the 50 substances and not for the whole 50, don´t know..., but I think, the style above is correct.)

( Zu den rund 50 psychoaktiven Substanzen liegen zudem umfassende und übersichtliche Synthesevorschriften und alternative Synthesestrategien mit Literaturangaben vor.)

Thanks Daniel ! Thanks Richard (Nicolas)!

Helvetica Chimica Acta, 2003, 86(7), 2610 - 2619 (http://angelfire.lycos.com/scifi2/lego/journals/trachsel2.pdf)

(http://angelfire.lycos.com/scifi2/lego/journals/trachsel2.pdf)
DOI:

10.1002/hlca.200390210 (http://dx.doi.org/10.1002/hlca.200390210)

Synthesis of Novel (Phenylalkyl)amines for the Investigation of Structure-Activity Relationships. Part 2.
4-Thio-Substituted [2-(2,5-Dimethoxyphenyl)ethyl]amines (=2,5-Dimethoxybenzeneethanamines)



Abstract

The 4-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines (=2,5-dimethoxybenzeneethanamines) and its -methyl analogs are known to act as potent 5-HT_2A/C ligands, which have, depending on their 4-substituent, agonistic or antagonistic character. Generally, compounds with a small lipophilic substituent typically are agonists and those with a larger lipophilic substituent predominantly antagonists or at least partial agonists. Since little is known about the transition and more information is needed about the structural requirements of the 4-substituent to control the functional activity, 12 novel 4-thio-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines were synthesized and spectroscopically characterized. Thus 2,5-dimethoxybenzenethiol (7) was converted to the thioether derivatives 8a-l with several alkyl, fluoroalkyl, alkenyl, and benzyl halides. Subsequent Vilsmeier-formylation afforded the benzaldehydes 9a-l, condensation with MeNO₂ the nitroethenyl derivatives 10a-l, and reduction with AlH₃ the desired (2-phenylethyl)amines 11a-l.

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Helvetica Chimica Acta, 2003, 86(8), 2754 - 2759 (http://angelfire.lycos.com/scifi2/lego/journals/trachsel3.pdf)

(http://angelfire.lycos.com/scifi2/lego/journals/trachsel3.pdf)
DOI:

10.1002/hlca.200390224 (http://dx.doi.org/10.1002/hlca.200390224)

The DOI is not working although it is from the publisher's homepage.



Synthesis of Novel (Phenylalkyl)amines for the Investigation of StructureActivity Relationships, Part 3
4-Ethynyl-2,5-dimethoxyphenethylamine (=4-Ethynyl-2,5-dimethoxybenzeneethanamine; 2C-YN)

Abstract

An easy and efficient pathway for the preparation of 4-ethynyl-2,5-dimethoxyphenethylamine (=4-ethynyl-2,5-dimethoxybenzeneethanamine; 2C-YN; 1) was developed, an ethynyl analogue of the potent 5-HT_2A/C agonists, e.g., 4-iodo-2,5-dimethoxy-amphetamine (DOI; 2b). The ethynyl moiety was introduced by a Pd-catalyzed Sonogashira reaction of (trimethylsilyl)ethyne with N-(trifluoroacetyl)-protected 4-iodo-2,5-dimethoxyphenethylamine (7) in almost quantitative yield within only 1 h. Removal of the Me₃Si group was accomplished with Bu₄NF. Final N-deprotection by NaOH treatment afforded the novel phenethylamine 1 in an overall yield of 88%.