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#39 2C-T

2,5-DIMETHOXY-4-METHYLTHIOPHENETHYLAMINE


SYNTHESIS: A solution of 149 g sodium thiosulfate in 300 mL H2O was vigorously stirred. To this there was added, over the course of 10 min, a solution of 43.2 g benzoquinone in 200 mL acetic acid. After an additional 1 h stirring at room temperature, all volatiles were removed under vacuum. The residual syrup slowly set up as crystals which, after grinding under brine, were removed by filtration and washed with additional brine. These were dissolved in MeOH, clarified by filtration through a Celite bed, and the clear filtrate stripped of solvent under vacuum. The yellow, powdery sodium 2,5-hydroxyphenylthiosulfate weighed 67 g when dry. This intermediate was dissolved in aqueous HCl (50 g in 200 mL H2O containing 400 mL concentrated HCl), cooled with an external ice bath, and treated with 250 g zinc dust added at a rate that kept the temperature below 60 °C. About 1.5 h were required, and caution must be taken concerning the poisonous hydrogen sulfide that evolves. An additional 50 mL concentrated HCl was added, and the aqueous phase decanted from the unreacted zinc metal. This was extracted with 6x100 mL Et2O, and these extracts were pooled, washed with brine, and the solvent removed under vacuum to yield 33.1 g of 2,5-dihydroxythiophenol as pale yellow needles with a mp of 118-119 °C.

A solution of 118.6 g KOH pellets in 200 mL H2O was placed under N2, and to it was added 24.0 g 2,5-dihydroxythiophenol. With vigorous stirring, there was then added 160 g methyl sulfate at a rate that maintained the temperature at about 60 °C. This took about 2 h. After the addition was complete, the mixture was held at reflux for 3 h, and allowed to stir at ambient temperature overnight. It was then filtered, and the filtrate extracted with 6x100 mL Et2O, the extracts pooled, washed with 2x50 mL brine, dried over anhydrous Na2SO4, and the solvent removed under vacuum. The residue was distilled at 86-88 °C at 0.04 mm/Hg to provide 25.9 g of 2,5-dimethoxythioanisole as a white oil that crystallized on standing. Its mp was 33-34 °C. An alternate preparation of this compound follows the direct methylation of 2,5-dimethoxythiophenol (see under 2C-T-2 for the preparation of this common intermediate) with methyl iodide.

To 40 mL dry CH2Cl2 there was added 6.07 g 2,5-dimethoxythioanisole, and this was cooled to 0 °C under N2. To this well stirred solution there was added 13.02 g stannic chloride over the course of 2 min. This was followed by the drop-wise addition of dichloromethyl methyl ether over 5 min, and the reaction mixture allowed to stir for an additional 15 min. After returning to room temperature, it was stirred for an additional 1 h. The reaction mixture was poured over 15 g ice, and the organic phase separated, washed with 3x25 mL 3 N HCl, with 3x50 mL brine and, after drying over anhydrous Na2SO4, the solvent was removed under vacuum. The residue was a solid and, after recrystallization from MeOH/H2O, gave 5.86 g 2,5-dimethoxy-4-(methylthio)benzaldehyde with a mp of 95-97 °C. Purification via the bisulfite complex provided an analytical sample with mp of 99-100 C. Anal. (C10H12O3S) C,H,S. The malononitrile derivative (from equal weights of the aldehyde and malononitrile in EtOH with a drop of triethylamine as catalyst) was recrystallized from an equal volume of EtOH to give orange crystals with a mp of 185-186 °C. Anal. (C13H12N2O2S) C,H,N,S.

A solution of 2.1 g 2,5-dimethoxy-4-(methylthio)benzaldehyde in 7.5 mL nitromethane was treated with 0.45 g anhydrous ammonium acetate and held at steam bath temperature for 6 h. The deep red solution was stripped of solvent to give a residue that spontaneously crystallized. This was ground up under 12 mL MeOH, filtered, and washed with MeOH to yield, after air-drying, 1.7 g of 2,5-dimethoxy-4-methylthio-beta-nitrostyrene as orange solids. Recrystallization from EtOH provided rust-orange colored crystals with a mp of 165.5-166 °C. Anal. (C11H13NO4S) C,H,N; S: calcd, 12.56; found, 11.96.

To a gently refluxing mixture of 1.4 g LAH in 40 mL anhydrous THF under an inert atmosphere there was added, dropwise, 1.7 g 2,5-dimethoxy-4-methylthio-beta-nitrostyrene in 25 mL THF. The refluxing was continued for 18 h, and the stirring continued for another day at room temperature. There was then added 1.5 mL H2O (diluted with a little THF), 1.5 mL 15% NaOH, and finally 4.5 mL H2O. The white aluminum oxide salts were removed by filtration, and the filter cake washed with THF. The filtrate and washings were combined and stripped of solvent under vacuum yielding a straw-colored residue that crystallized (mp 81-92 °C without purification). This residue was dissolved in 25 mL IPA and neutralized with concentrated HCl. The slightly pink solution spontaneously crystallized. There was added 100 mL anhydrous Et2O, and the white crystalline mass of 2,5-dimethoxy-4-methylthiophenethylamine hydrochloride (2C-T) was removed by filtration, washed with Et2O, and air dried. The final weight was 1.0 g, and had a mp of 232-237 °C. Recrystallization from EtOH provided an analytical sample with mp 240-241 °C. IPA was not a good recrystallization solvent. Anal. (C11H18ClNO2S) C,H,N,S.

DOSAGE: 60 - 100 mg.

DURATION: 3 - 5 h.

QUALITATIVE COMMENTS: (with 60 mg) Poetry was an easy and natural thing. Both the reading of it and the writing of it. This is a potential MDMA substitute since it opens things up but it doesn't do anything to get in the way.

(with 75 mg) I am already aware at a quarter of an hour into it! It develops very quickly but very quietly. There are no visuals at all but, rather, a tactile sensitivity, with warm close feelings. This could be very erotic. There is some fantasy to music, but nothing very demanding. The viewing of pictures doesn't do much either. The drop-off was extremely relaxed, with a good body feeling. At the fifth hour I was able to drift into an excellent, deep sleep with busy dreams. In the morning I felt refreshed and active, without apparent deficit.

(with 75 mg) I got up to a thin and fragile plus two, but there was a continuing feeling of a hooded cloak brought down over my head. Nothing obvious--it is transparent--but it somehow separated me from everything around me. I do not think the overall experiment was worth it.

(with 100 mg) Material all right, but a little bit along the lines of a 'generic' psychedelic effect. Sharper edges than 2C-B. The one true negative, which has been pretty consistent with this drug, is that there is a certain emotional removal. One teeny step removed. One is connected with feelings, certainly, but there is a tendency for the intellect to be more evident, in me, than the heart. All this is moderately so. Nothing extreme. Pretty good material, but there are more inter-esting ones. However, if you are looking for a really short one, this is one of the answers. For most people. For me, it's still around 5 to 6 hours long. I wish we had more shorties, indeed.

(with 125 mg) There was some physical tummy uncertainty, but once that was past, talking was extremely easy. This is probably really psychedelic, but I am not really sure why, as there is not much in the way of visuals. Dropping was noted just after hour number three, and I was at baseline three hours later.

EXTENSIONS AND COMMENTARY: The earliest work with the sulfur atom was with the three-carbon chain materials, the ALEPHs. It was only after a considerable time of working with them, and trying to come to peace with their property of being so different from person to person as to potency, that the two-carbon homologues were looked at. Although the first of these (this compound, called 2C-T) was prepared at the same time as ALEPH-1, there was a lapse of about four years between their trials. The relatively low potency of 2C-T was a bit discouraging. But the methodical pursuit of the higher 2C-T's (to parallel the higher ALEPHs) proved to be a treasure house, and they have been explored much further than any of the ALEPHs.

A note on the RTS in 2C-T. Many, in fact most, of the 2C's have their name based on the last letter of the amphetamine prototype. 2C-B from DOB, 2C-C from DOC, 2C-I from DOI, 2C-N from DON, etc. And since the original name for ALEPH-1 was DOT (the desoxy- and a thiomethyl group at the 4-position), the 2C-T naming followed this general pattern. And as a note on the subsequent numbering, they (both the ALEPHs and the 2C-T's) are assigned numbers as they are thought up. There is no structural significance in the number but they have been, like the houses on the streets in residential Tokyo, assigned numbers in strict historical order, documenting the sequence of construction rather than the relative position down the side of the street.

Both of the homologous mono-ethoxy Tweetios of 2C-T have been synthesized and evaluated. The 2-EtO-homologue of 2C-T is 2-ethoxy-5-methoxy-4-methylthiophenethylamine, or 2CT-2ETO. The benzaldehyde (2-ethoxy-5-methoxy-4-(methylthio)benzaldehyde) was an oil, the nitrostyrene intermediate had a melting point of 137-138 °C, and the final hydrochloride a melting point of 215-216 °C. The effects were felt very quickly, and there was a blurring of vision. However, the highest dose tried, 50 milligrams, was not able to produce a greater-than-plus one state, and what did occur, lasted for only 4 hours.

The 5-EtO-homologue of 2C-T is 5-ethoxy-2-methoxy-4-methylthio-phenethylamine, or 2CT-5ETO. The benzaldehyde (5-ethoxy-2-methoxy-4-(methyl-thio)benzaldehyde) was impure, and had a melting point of about 66 °C, the nitrostyrene intermediate a melting point of 133-134 °C, and the final hydrochloride a melting point of 184-185 °C. There was a body awareness and modest eyes-closed visuals following the use of 30 milligrams of 2CT-5ETO. The experience was quiet, peaceful, contemplative, and insightful. The duration was perhaps 15 hours and Halcion was needed to allow sleep. There were a lot of dreams, and the next day was restful.


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