Characterization of the synthesis of N,N‐dimethyltryptamine by reductive amination using gas chromatography ion trap mass spectrometry

Abstract

The present study established an impurity profile of a synthetic route to the hallucinogenic N,N-dimethyltryptamine (DMT). The synthesis was carried out under reductive amination conditions between tryptamine and aqueous formaldehyde in the presence of acetic acid followed by reduction with sodium cyanoborohydride. Analytical characterization of this synthetic route was carried out by gas chromatography ion trap mass spectrometry using electron- and chemical-ionization modes. Methanol was employed as a liquid CI reagent and the impact of stoichiometric modifications on side-products formation was also investigated. Tryptamine 1, DMT 2, 2-methyltetrahydro-β-carboline (2-Me-THBC, 3), N-methyl-N-cyanomethyltryptamine (MCMT, 4), N-methyltryptamine (NMT, 5), 2-cyanomethyl-tetrahydro-β-carboline (2-CM-THBC, 6) and tetrahydro-β-carboline (THBC, 7) have been detected under a variety of conditions. Replacement of formaldehyde solution with paraformaldehyde resulted in incomplete conversion of the starting material whereas a similar replacement of sodium cyanoborohydride with sodium borohydride almost exclusively produced THBC instead of the expected DMT. Compounds 1 to 7 were quantified and the limits of detection were 28.4, 87.7, 21.5, 23.4, 41.1, 36.6, and 34.9 ng mL(-1), respectively. The limits of quantification for compounds 1 to 7 were 32.4, 88.3, 25.4, 24.6, 41.4, 39.9, and 37.0 µg mL(-1), respectively. Linearity was observed in the range of 20.8-980 µg mL(-1) with correlation coefficients > 0.99. The application holds great promise in the area of forensic chemistry where development of reliable analytical methods for the detection, identification, and quantification of DMT are crucial and also in pharmaceutical analysis where DMT might be prepared for use in human clinical studies.

Synthesis and Evaluation of Ciprofloxacin-Nitroxide Conjugates as Anti-Biofilm Agents

“…To begin, the carboxylic acid of ciprofloxacin 2 was protected by conversion to the ethyl ester derivative 5 , by following previously documented methodologies [44]. Using typical reductive amination conditions [45], a methanol solution of the protected ciprofloxacin 5 with TEMPONE 6 and acetic acid (4 equivalents) was treated with NaBH 3 CN. Acetic acid is often used for reductive amination reactions with ketones to catalyze the formation of the imine intermediate [46].…”

Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials

“…45 Other methods of synthesizing DMT have also been described, for example, demethylation of N,N,N-trimethyltryptammonium iodide, dimethylamination of 3-(2-bromoethyl)indole, or reductive amination of tryptamine with formaldehyde and sodium cyanoborohydride. 37,46,47 In the 1950s, an improved general route for the synthesis of tryptamines was developed by Speeter and Anthony, 48 and this method was used by Szára to produce DMT for the first human studies. 12 Although Szára employed DMT as the aqueous hydrochloride salt, the hemifumarate salt of DMT has been used in more recent human studies.…”

“…Manske who employed methyl iodide to alkylate the tryptamine side chain to obtain a mixture of the primary, secondary, and tertiary bases from which DMT was ultimately isolated 45 . Other methods of synthesizing DMT have also been described, for example, demethylation of N,N,N ‐trimethyltryptammonium iodide, dimethylamination of 3‐(2‐bromoethyl)indole, or reductive amination of tryptamine with formaldehyde and sodium cyanoborohydride 37,46,47 . In the 1950s, an improved general route for the synthesis of tryptamines was developed by Speeter and Anthony, 48 and this method was used by Szára to produce DMT for the first human studies 12 .…”

Test purchase of new synthetic tryptamines via the Internet: Identity check by GC-MS and separation by HPLC

“…Some articles report on a comparison of separation methods including HPLC, CE and GC for tryptamines (Wang et al, 2008;Brandt and Martins, 2010).…”

“…Additionally, literature about the synthesis and cytotoxic properties (Salikov et al, 2015) as well as characterization of psychotropic tryptamines is available (Brandt et al, 2010;Tearavarich et al, 2011;Brandt et al, 2012;Elliott et al, 2013). Hsiao and co-workers reported on the simultaneous separation and detection of phenetylamine and tryptamine derivatives using HPLC-UV and LC/ESI MS (Hsiao et al, 2009).…”