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)
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)
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-HT2A/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.
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-HT2A/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%.