Erowid 4-Acetoxy-DET Vaults : 4-Acetoxy-DET / Ethacetin Degradation

This reverberating psychedelic giclee print is a gift for a
$500 donation to Erowid. 12" x 12", stretched on canvas, the
image wraps around the sides of the 1" thick piece. Signed
by artist Vibrata, and Erowid founders Earth & Fire.

4-Acetoxy-DET / Ethacetin Degradation Investigation

by Murple

V 1.1 July 4, 2003

With invaluable contributions by Alexander Shulgin, DrWild, Gloggawogga, Meilikhios, Morninggloryseed, RandomStu, the staff of Erowid, and most of all, the nameless chemist who made this possible.

[Editor's Note: Murple uses the term "ethacetin" based on his suggested nomenclature, which is described in the second half of this article.]

On May 1, 2001, a research chemical manufacturing company introduced 4-acetoxy-diethyltryptamine (4-AcO-DET, AKA ethacetin) to its product inventory. Several months earlier, the company had introduced 4-AcO-DIPT. The reasoning for producing the much more difficult to synthesize acetate esters was that it was theorized that they would be structurally more stable and have longer shelf lives than the corresponding free phenols (4-hydroxy-DIPT and 4-hydroxy-DET).

It was theorized by most people that these 4-acetoxy-tryptamines would saponify to the 4-hydroxy analog in the body, just as psilocybin (4-phosphoryloxy-DMT) is believed to convert to psilocin (4-hydroxy-DMT) in vivo. Described effects are certainly about the same. However, it seems that this may not be entirely true. According to Alexander Shulgin, "In the case of psilocybin to psilocin, this saponification is essential for activity, as the phosphate ester is far too polar to get across the blood-brain barrier. But this problem need not exist with the acetate ester. I have explored the 4-hydroxy-DET but I am more familiar with the 4-hydroxy-DIPT. It is of a rather rapid onset implying possible absorption directly from the stomach. However, in a group study with the corresponding ester 4-AcO-DIPT, we felt that it had an even faster onset and perhaps a increased potency. This would suggest that it might be considered an active drug in its own right rather than simply a precursor to the active drug 4-HO-DIPT."

Several months after the appearance of ethacetin on the market, some people began to report it breaking down to a black goo. Below is a series of images showing the various stages of this breakdown process.

The material changed from the original sandy/tan powder to a black tarry goo at different rates depending on storage. Of the samples in the image above, the one on the left is representative of the original material. The middle shows an intermediate state of decomposition. This sample reportedly had been stored for about five months at a temperature of approximately 60°F (15°C) in a plastic bag. The specimen on the right shows the black goo state of composition which many samples have become after a few months or years. The sample shown here broke down to this final state in only three months, perhaps due to being stored in a car and consequently being exposed to excessively warm temperatures.

Erowid listed the photos of the decomposed product as "oxidized," indicating the most popular theory as to what was happening to the product. However, the problem is that oxidized tryptamines generally become inactive. Evidence seemed to indicate something else going on.

Surprisingly, many people were reporting that this black goo was every bit as active as the original material. One person reported "I have tested fresh 4-AcO-DET when they sent out the samples all those years ago that was off-white and I have tested brown, degraded 4-AcO-DET I got as a gift from a friend and there is no noticable loss/change in potency or effect between the two." Another person, working with similarly degraded ipracetin goo said "I couldn't detect a drop in potency or a qualitative change - I did notice however that I was more irritable in my after trips than in the beginning and wasn't getting the profound zen-like peace of mind I had achieved the first times. I cannot say however whether this has anything to do with the 'changing into goo' process or just me in a bad patch at the time. I also want to point out that initially the solution wasn't smelly but as it darkened the smell become horrible." A third person reported "I had some 4-Aco-DET of known potency, foolishly left it unfrozen till it oxidized into black goo. When I tried smoking the black goo, I found that a tiny amount brought on an immediate and intense rush, then settled into a approximately 2 hour experience much like oral ingestion of the non-oxidized substance. I've had it confirmed by one other researcher that smoking the oxidized substance supplies an immediate rush of great intensity."

What could be going on? It was very surprising to me that this material could be undergoing such a visible physical change without seeming to lose activity. I discussed the situation with Dr. Shulgin. He agreed that based on visual appearance and the succeptibility of tryptamines to oxidation that it was a good hypothesis, but he was intrigued by my suggestion that rather than oxidation, some other process could be going on which was resulting in an active breakdown product. He speculated, "In the 4-hydroxy indole world, an obvious quinonic product would be the cross-conjugated product with the loss of the hydrogen on the hydroxy as well as the hydrogen on the indolic nitrogen. This compound would certainly be colored and, still having no polar locations, might be OK to cross the BBB [blood brain barrier]. Once inside the brain, it could be reduced to the parent hydroxy tryptamine or an even more appealing explanation might be that the absorbed 4-AcO-DIPT (4-AcO-DET in your immediate example) might, after loss of the acetyl group once inside the brain, be oxidized to this very quinonic product and it just might be the true active factor for both original forms!" If this had been true, it may have required some major revision in what we believe about the way drugs like psilocybin work. Further data seems to point in yet another direction, however.

I was able to find a sympathetic chemist with GCMS testing capability who offered to do a test on some of the decomposed goo, and a volunteer who had some of the black goo which he offered to donate as a sample for testing. After making the proper go-together motions and waving my magic wand, I was able to obtain the GCMS analysis results presented here.

The cover letter (see link below) explains the findings in more technical terms, but the short version is that the majority of the goo seems to consist of the free phenol (ethocin, AKA 4-HO-DET or CZ-74; "A" in the graphs below). In addition to ethocin, there is also some remaining ethacetin ("B"), as well as two analogous substances where the amino (NH) group on the secondary tryptamine ring has been replaced with a different group. These two substances ("C" and "D" in the graphs) have no names yet and are of unknown activity. It also is unknown whether these are breakdown products and/or impurities from the original synthesis. Several unidentified peaks were found which may or may not have much significance.

One person with some medical forensics knowledge saw the analysis results and remarked "Regarding the color, my guess would be that the color would be the result of some high molecular weight polymers that could very well be constituents of the goo. The carbonyl group in compound "D" is in a position that might lend itself to some degree of photoactivity. This compound, upon exposure to light, might be susceptible to polymerization."

The breakdown to black goo has been reported with both ethacetin and 4-AcO-DIPT free bases, but not universally. Some people who have kept their product airtight in a freezer have not had any product degradation even after nearly two years. I have even heard of at least one sample which was accidentally left exposed to summer conditions (approximately 85-95° F with high humidity) for two months protected by nothing more than a plastic Ziploc baggie and a white paper envelope, but which has since been kept refrigerated; this sample has no visible signs of decomposition, although no chemical or bioassay tests have been done to test that particular sample.

One person, working with ipracetin and ethacetin, believes temperature is in fact the key. He reports "I diluted them in 10% aqueous ethanol in an amber glass vial and put them in the freezer. I watched the [ipracetin] taking on a green tinge then [a] frankly glaucous green (but still transparent) before eventually turning into a black stinky mess over a period of kind of like two months I guess. I vaguely recall than the [ethacetin] took a bit longer (half a month I think) to eventually become completely black. [...] Also after it had reached the point of a dark goo it didn't degrade any further. Once I realized my [ethacetin] had gone 'bad' I dissolved it in a great amount of water (I didn't care much for the little sample I had) and could observe its 'real color'. It was in fact a brown solution with orange/yellow reflects whch didn't change anymore until I discarded it too - [ipracetin] being a dark green olive solution instead. [...] I also want to point out regarding the [ipracetin] solution that I had given some to a friend in exactly the same amber glass vial as me the very day I dissolved it. He left it in his drawer; it was summer time and I recall that temperature was [approximately] 23°C. He checked again later and it had turned completely black in a matter of hours. Clearly temperature is a key issue here."

Another person reports "[Ipracetin] (not sure if it was salt or freebase) was kept in an airtight vial frozen for 16 months and and room temperature for 2 months. No noticable change in color or potency. [Ethacetin] HCl salt was also kept in an airtight vial frozen. After 9 months there was no noticable change in color potency."

While temperature may in fact be a critical factor here, it is also possible that it is something else. Keep in mind that the first sample discussed in this paragraph was stored in solution, and also consider the example in the previous paragraph where a dry powder stored in only a plastic bag in high temperatures and humidity did not turn into the goo.

The good news is that the breakdown product is mostly ethocin, which is itself an active substance. Unfortunately, according to Shulgin, "the 4-hydroxy tryptamine family is quite susceptable to it [oxidation]. Psilocin is quite unstable as the free base, especially if there is some inorganic base present. So the purity can call the stability shots as well." This likely applies to ethocin and 4-HO-DIPT (iprocin) free bases as well. If you have any of these 4-substituted tryptamines in free base form, you should take extra care to keep it in optimal conditions - air tight, dry, and very cold. Perhaps store with an oxygen absorbant pack and silica gel dessicant if possible. If you have some chemistry skills, conversion to a more stable salt form may be wise. Unfortunately, not being a chemist, I can't give specific information on how to do this other than to point out that "base plus acid equals salt."

Here are the results from the chemical analysis. The NMR analysis included with the product at time of sale is included for comparison purposes.

Footnote on Nomenclature of Psilocin Analogues #

Some notes on the nomenclature of the psilocin analogues used in this paper are in order. These names were devised mostly by myself (except for the names of the two natural alkaloids and "iprocin"). I can't claim exclusive credit, since I got much feedback from others. They were conceived with the names of the naturally occuring mushroom alkaloids as the base forms and by applying a principle of analogous names for analogous substances. This should be clear by reading down the columns in the chart below. In the case of the acetate esters, an "-acet-" was inserted into the names to indicate the presence of the acetyl ester group in the molecule.

Unsubstituted at 4 position	Free Phenol 4-Hydroxy	Acetate Ester 4-Acetoxy	Phosphoryloxy Ester 4-Phosphoryloxy
DMT	Psilocin	Psilacetin	Psilocybin
DET	Ethocin	Ethacetin	Ethocybin
DIPT	Iprocin	Ipracetin	Iprocybin
MIPT	Miprocin	Mipracetin	Miprocybin

Note that there are older lab code-names for some substances re-named here. Chiefly, the lab code-name for ethocin was CZ-74 and the lab code for ethocybin was CEY-19. These codes were given by the inventors of the substances in the late 1950s, Albert Hofmann and his partner F. Troxler working at Sandoz. These code-names are also found in scientific literature on human clinical trials with CZ-74 conducted in the 1960s by German researchers Hanscarl Leuner and G. Baer.

When ethacetin and ipracetin hit the market, they were soon given names like "iprocetyl" and "ethylacybin," all based on the same concept of deriving names from psilocin. "Ethylacybin" was my own miscreation, and "iprocetyl" went back even further to an early experimenter with the drug. The flaw with "ethylacybin" was that it was only one letter off from what was an earlier proposed name for the phosphoryloxy ester ("ethylocybin" for 4-PO-DET). The flaw with "iprocetyl" was that it didnt really fit the pattern of the natural alkaloid names. While working on this project investigating the breakdown of the acetate ester of ethocin, it became apparant that a newer and more consistent naming scheme was necessary.

After discussion with various members of the Waka Pacha forums and with Dr. Shulgin, and going through several variations on possible names, the naming scheme given here was born. After checking with Shulgin and various online chemistry databases to ensure none of these names were already in use for other substances, I settled on the names in the chart above. Considering his stature in the scientific community and his vast experience with naming new chemicals, I submitted the final proposals to Shulgin for his approval. He found the names to be logical and appropriate, and agreed with the idea of giving these chemicals names which are easy to pronounce so as to minimize the urge to come up with slang names: "I agree with you that these new tryptamines would be less offensive if things like 'foxy' were not used." I have long wondered if 5-MeO-DIPT would ever have reached the outrageous popularity it attained if it had not been given a sexy nickname like "foxy." Perhaps it would still be legal if it had a less glorifying name. We'll never know for sure, but hopefully we can avoid a repeat.

Credits

Anonymous. GCMS analysis.
Erowid. 4-Acetoxy-DET 3 Oxidized Samples
Morninggloryseed. Project assistance and miscellaneous data collection.
Shulgin, Alexander. Private E-mail: Sat, 1 Mar 2003 12:45PST.
Shulgin, Alexander. Private E-mail: Fri, 11 Apr 2003 18:46PST.
Toad. "4-Acetoxy-DET Primer." Entheogen Review; Vol. 10, No. 3 (Autumn 2001).
Various contributors to the Waka Pacha forums.