3,4,5-Trimethoxyphenyl-ethylamine

Mescaline sulphate [2-(3,4,5-trimethoxyphenyl)ethylamine sulphate] [5967-42-0] M 309.3 m 183-184°. Crystd from water. 

Mescaline [54-04-6] (2-(3,4,5-trimethoxyphenyl)ethylamine) is the active ingredient in mescal buttons (peyotl or peyote), which are the dried tops of the Mexican dumpling cactus l ophopora wilhamsi. Mescaline produces visual hallucinations on ingestion. Its possible use as a psychotomimetic drug in the field of mental health has been studied (see Alkaloids Psychopharmacologicalagents). 

Another naturally occurring drug that is similar to amphetamine can be found in the cactus Lophophora williamsii. Extracts are used to prepare a drink called peyote that contains 3,4,5-trimethoxyphenyl-ethylamine(the meth and phenyl point to a molecule that is quite lipid soluble). Known as mescaline, this compound is structurally similar to the catecholamines dopamine and norepinephrine but seems to act more directly upon serotonin receptors because of the presence of the meth-oxy groups on the molecule. This feature of the compound s structure would make the compound more fat-soluble and therefore better able to enter the brain quickly and may explain... 

Sodium cyanide reacts with alkyl bromides by the SN2 mechanism. Reduction of the cyano group with lithium aluminum hydride yields a primary amine. This reveals the structure of mescaline to be 2-(3,4,5-trimethoxyphenyl)ethylamine. 

Like any substituted arene, this compound may be named as a substituted alkyl chain, which in this case is an amine. On the aromatic ring itself, the "3", "4 , and "5" positions contain methoxy groups (-OCHa). Thus the lUPAC name of mescaline is 2-(3,4,5 trimethoxyphenyl)ethylamine. 

As I have pointed out before, street samples do not always contain what is claimed. They are often mixtures, and they may hold components which are unknown to us. In such cases, GC-MS is of great help. A product which was submitted to our laboratory as Mescaline did not contain a trace of 3,4,5-trimethoxyphenyl-ethylamine but instead 2 different organic bases could be isolated and identified by GC-MS, Fig. 3 gives the mass spectrum of the major component which led to its identification as l-(l-phenyl)--cyclohexylpiperidine or phencyclidine, the active ingredient of Sernyl, the so-called peace drug. 

While mescaline is a simple 2-phenethylamine derivative, the addition of an alpha-methyl group to the side chain yields Structure 8 (TMA). This simple hybrid of the structures of mescaline and amphetamine retains the hallucinogenic effects of mescaline but possesses about twice the potency of the latter (174,200). Addition of the alpha-methyl to other 3,4,5-substituted compounds generally brings about an approximately twofold increase in potency. The addition of an alpha-methyl to 2,4,5-substituted compounds, however, may dramatically increase activity. For example, 2-(2,4,5-trimethoxyphenyl) ethylamine apparently is clinically inactive (195). Addition of an alpha-methyl gives TMA-2 (Table 1), with 20 times the potency of mescaline. However, the addition of an alpha-methyl does not significantly increase in vitro receptor affinity in either 3,4,5-or 2,4,5-series (72,78). Thus it is probable that the alpha-methyl may confer metabolic stability in vivo. It could also be speculated that this protection is more important in the 2,4,5-substituted series than in 3,4,5-substituted compounds. 

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