#127 Methyl-dob; 4-bromo-2,5-dimethoxy-n-methylamphetamine

SYNTHESIS: To a solution of 6.0 g of the free base of 2,5-dimethoxy-N-methyl-amphetamine (see recipe under METHYL-DMA) in 30 mL glacial acetic acid there was added, dropwise and with good stirring, a solution of 5.5 g bromine in 15 mL acetic acid. The reaction became quite warm, and turned very dark. After stirring an additional 45 min, the mixture was poured into 200 mL H2O and treated with a little sodium hydrosulfite which lightened the color of the reaction. There was added 20 mL concentrated HCl, and the reaction mixture was washed with 2x100 mL CH2Cl2 which removed most of the color. The aqueous. phase was made basic with 25% NaOH, and extracted with 3x100 mL CH2Cl2. The removal of the solvent from the pooled extracts under vacuum gave 1.8 g of an oil which was dissolved in 10 mL IPA, neutralized with concentrated HCl, and diluted with 100 mL anhydrous Et2O. No crystals were obtained, but rather an oily and somewhat granular insoluble lower phase. The Et2O was decanted, and the residue washed by grinding up under 3x100 mL Et2O. The original decanted material was combined with the three washes, and allowed to stand for several h. The product 4-bromo-2,5-dimethoxy-N-methylamphetamine hydrochloride (METHYL-DOB) separated as fine white crystals which weighed, after filtering and air drying, 0.3 g and had a mp of 149-150 deg C. The Et2O-insoluble residue finally set up to a pale pink mass which was finely ground under a few mL acetone. Filtration and air drying gave a second crop of product as 0.9 g of pale lavender solids, with a mp of 143-145 deg C.

DOSAGE: greater than 8 mg.

DURATION: probably rather long.

QUALITATIVE COMMENTS: (with 8.0 mg) At an hour and twenty minutes, I was suddenly quite light headed. An hour later I must say that the effects are real, and generally good. I am spacey Q nothing tangible. And a couple of hours yet later I am still aware. My teeth are somewhat rubby, and as things have been pretty steady for the last three hours, this will prove to be long lasting. There are a lot of physical effects that may be kidding me into providing myself some of the mental. At the sixth hour, I find that this is almost entirely physical. My teeth are tight, there is a general physical tenseness, my reflexes seem exaggerated, and my eyes are quite dilated. All of these signs are lessened by the eighth hour, and do not interfere with sleep at the twelfth hour. There is no desire to proceed any further, at least at the present time. Mental (+) physical (++). Next day, slight impression of persistence of toxicity.

(with 10 mg) Nothing psychedelic, but awfully hard on the bod. The next day (24 hours later) I had a severe response to 5 milligrams of psilocybin.

EXTENSIONS AND COMMENTARY: The mention above, of the 10 milligrams of METHYL-DOB followed by 5 milligrams of psilocybin, leads to some interesting speculation. The usual pattern that is seen when two psychedelic drugs are taken too closely together is that the second experience is less effective than would have been expected. This is the property that is called tolerance, and it is frequently seen in pharmacology. The two exposures may be to a single drug, or they may be to two different drugs which usually have some properties in common. It is as if the spirit of the receptor site had become a little tired and needed a while to rest up and recuperate. When there is a demand for a repeat of full effectiveness, the user will customarily increase the dosage of the drug that is used. It is one of the built-in protections, in the area of psychedelics that, after one experience, you must wait for a period of time to lose the refractoriness that has set in.

The measure of the degree of tolerance that can be shared between different drugs, called cross-tolerance, can be used as an estimate of the similarities of their mechanisms of action. In other words, if A and B are somehow seen by the body as being similar, then a normally effective dose of A will make a next-day's normally effective dose of B weaker than expected. Or not active at all. And B will do the same job on A. If two drugs are different in their ways of doing things in the body, there is most often no cross-tolerance seen. This was described for MDMA and MDA, and is the basis of the argument that they act by distinctly separate mechanisms. A person who used what would be held as an active dose of MDMA for several days lost all response to the drug. He was tolerant to its effects. But an exposure to an effective dose of MDA at the time that tolerance to MDMA was complete, provided a normal response to the MDA. The drugs are not cross-tolerant and the body recognizes them as distinct individuals.

But for one drug to promote, or to exaggerate, the effect of another is called potentiation, and can be a clue to the dynamics going on in the brain or body. Here, admittedly in only a single report, METHYL-DOB had somehow sensitized the subject to a rather light dosage of psilocybin. But there have been other reports like this that I have heard of, from here and there. I have been told of an experiment with the dextro-isomer of DOM (this is the inactive optical isomer) at a level that was, not surprisingly, without any effects. The researcher had a severe reaction the following day with what was referred to as "poor" hashish. A similar form of potentiation has been commented upon under the recipe for TOMSO, where an inactive drug, and a most modest amount of alcohol, add together to create an unexpectedly intense intoxication. But note that in each of these cases, it is a phenethylamine interacting with a non-phenethylamine (psilocybin is an indole, hashish is a non-alkaloid terpene thing, and alcohol is, well, alcohol).

The bottom line with METHYL-DOB is, as with the other N-methylated psychedelics, that it is way down in potency, and probably not worth pursuing.

#128 METHYL-J; MBDB; EDEN;

2-METHYLAMINO-1-(3,4-METHYLENEDIOXYPHENYL)BUTANE;

N-METHYL-1-(1,3-BENZODIOXOL-5-YL)-2-BUTANAMINE

SYNTHESIS: A solution of 0.12 g mercuric chloride in 180 mL H2O was added to 5 g aluminum foil that had been cut into 1 inch squares, and amalgamation allowed to proceed for 0.5 h. The gray cloudy aqueous phase was decanted, and the resulting aluminum washed with 2x200 mL H2O. After shaking as dry as possible, there was added, in sequence, a solution of 7.6 g methylamine hydrochloride in an equal weight H2O, 23 mL IPA, 18.3 mL 25% NaOH, 6.72 g 1-(3,4-methylenedioxyphenyl)-2-butanone (see under the recipe of J for its preparation), and finally 44 mL additional IPA. The mixture was occasional swirled, and cooled externally as needed to keep the temperature below 50 deg C. After the reduction was completed (no metallic aluminum remaining, only gray sludge), it was filtered and the residues washed with MeOH. The combined filtrate and washes were stripped of organic volatiles under vacuum, the residue treated with 100 mL Et2O, and this was extracted with 2x50 mL 3 N HCl. After washing the pooled aqueous extracts with 3x100 mL CH2Cl2, they were made basic with an excess of 25% NaOH and extracted with 5x50 mL CH2Cl2. Drying of these extracts with anhydrous MgSO4 and removal of the solvent gave a residue that was distilled at 88 deg C at 0.08 mm/Hg to give a colorless oil that was dissolved in IPA and neutralized with concentrated HCl. The solids that separated were removed by filtration, Et2O washed, and air dried to provide 6.07 g 2-methylamino-1-(3,4-methylenedioxyphenyl)butane hydrochloride (METHYL-J or MBDB) as white crystals with a mp of 156 deg C. Anal. (C12H18ClNO2) C,H,N. Reductive amination of the butanone with methylamine hydrochloride in MeOH, employing sodium cyano-borohydride, gave an identical product but in a smaller yield.

DOSAGE: 180 - 210 mg.

DURATION: 4 - 6 h.

QUALITATIVE COMMENTS: (with 210 mg) Generally very, very friendly, very quiet effect. I can read easily, but looking at pictures in most books is relatively meaningless. Distinct de-stressing effect, to the point where it's too much trouble to set out to do anything at all, really. There is just no drive, and it isn't even bothersome to be missing it. Do I like it? Yes, very much. Feel that I've just begun to explore it, though. Would I consider this material in therapy? Well, sure, it's worth trying. Destressing would be excellent, and better than MDMA in some ways, but the empathy and intuition levels have yet to be explored in a therapy setting. I feel that they may be somehow lower.

(with 210 mg) Onset rapid. Alert 20 minutes, and to a +2.5 at 30 to 35 minutes. No physical symptoms, i.e., teeth clench, no stomach problems. Good visual enhancement; eyes open Q bright colors Q no visuals with eyes closed. No 'cone of silence' that I get with MDMA (and enjoy), otherwise I'm not sure I could tell which was which if I took them blind.

(with 210 mg and a 50 mg supplement) RTasted perfectly rotten. Suspect I was getting some type of alert in 5 minutes (I often get one quickly with MDMA) and at 30 minutes, a full blown high developed rather abruptly. It would be difficult to describe the high. I suspect it is the lack of language for the phenomenon. I would describe it somewhat like an alcohol high without the disabling side effects of confusion, slurring, staggering and etc. The high never got any more intense than at that 30 minute point and with a noticeable drop in another hour, I took a 50 mg supplement. I enjoyed the high. I relaxed with the material. However, it did not seem to have the same qualities as MDMA, in that it was not as stimulating, and it had very little visual activity. I talked with others, but found it easy to lie down and relax. There was some jaw-clenching towards the end, and I had considerable nystagmus at the peak which I could control. After the experience, I did not want to drink alcohol very much (sell it as a substitute for EtOH!).

(with 210 mg and a 70 mg supplement) RI begin to feel the rush at 20 minutes, increasing rapidly. Very much like MDMA, only more intense intoxication. Otherwise same symptoms: intense euphoria that I call a feeling of grace, soft skin, voices, youthful appearance, animated discussions, feelings of great closeness to others. I start to drop noticeably at less than an hour and a half into it, but I delayed a supplement until the hour and fifty minute point. It does not get me back to the original intoxication. However, it is very nice, very much like MDMA. Only difference is that there seems to be more quietness, less inclination to talk than with an MDMA supplement. My conclusion: Seems an excellent substitute for MDMA, Next time may try somewhat lower amount, supplement sooner.

EXTENSIONS AND COMMENTARY: An observer who was familiar with the outwardly apparent effects with groups experimenting with MDMA felt that, although most subjects commented favorably in their comparisons of METHYL-J with MDMA, there was lacking some of the spontaneity, the warmth, and the clear intimacy of the latter drug. The dosage range explored is remarkably tight, attesting to a consistency of response. The typical supplement used, if any, was 70 milligrams or less, just before the two hour point. This indicates a chronology similar to that of MDMA, and about two thirds the potency.

The arguments that weigh the use of the code name of MBDB against the use of METHYL-J are present in the recipe for BDB (or J). But what is the source of this H, I, J, K naming thing that I have called the Muni Metro?

First, a little bit of local color. In San Francisco, there is a public transportation called the S.F. Municipal Metropolitan System complex that has integrated an underground street-car system that emerges above ground and connects with a bus network. A number of the street-car lines fan across the city to the outer reaches which are called the Avenues. These lines are named by sequential letters. There is the J Church Street line, the K Ingelside line, the L Taraval line, the M Ocean line, and the N Judah. And in the pharmacological complex that involved the lengthening of the aliphatic chain, there were two coincidental benchmarks in the names that were proposed. Those without an alpha-substituent (no carbon atoms at the position alpha to the amine group, the phenethylamines) were originally called the H compounds. H stood for "homopiperonylamine." And the first of those with the alpha-ethyl group there (two carbon atoms at the position alpha to the amine group) was familiarly called "Jacobamine" in recognition of a famous chemist who had set the synthetic wheels in motion.

It is quite obvious, that with one carbon atom lying on that alpha-position, you are precisely half-way between no carbons and two carbons. And there was one letter of the alphabet that lies precisely half-way between an H and a J. So, an natural naming pattern developed. The I compounds were already pretty well known by names such as MDA and MDMA and MDE, so I, and METHYL-I, and ETHYL-I, didn't have any appeal. But for the new, the alpha-ethyl compounds, why not call them the J-compounds? If it has a methyl on the nitrogen it will be METHYL-J and if it has an ethyl group it will be ETHYL-J. And in the next longer group, the 3-carbon propyl group on the alpha-position becomes the K family, and the 4-carbon butyl group located there, the L family. Each with its METHYL and ETHYL prefixes, if the nitrogen atoms are substituted with a methyl or and ethyl group. V'la, comme on dit en Français. Le systième Muni Metro. Plus simple.

#129 METHYL-K; 2-METHYLAMINO-1-(3,4-METHYLENEDIOXYPHENYL)PENTANE;

N-METHYL-1-(1,3-BENZODIOXOL-5-YL)-2-PENTYLAMINE

SYNTHESIS: The Grignard reagent of butyl bromide was prepared in anhydrous Et2O by the dropwise addition of 68 g n-butyl bromide to a well-stirred suspension of 14 g magnesium turnings in 500 mL anhydrous Et2O. When the exothermic reaction had stopped, there was added a solution of 60 g piperonal in about 100 mL Et2O, over the course of 1 h. After the exothermic addition was complete, the reaction mixture was held at reflux for several h, then cooled and decomposed by the addition of dilute HCl. The phases were separated, and the aqueous phase extracted with 2x75 mL CH2Cl2. The organics were combined and gave, after the removal of the solvents under vacuum, 84 g of 1-hydroxy-1-(3,4-methylenedioxyphenyl)pentane as a yellow liquid. This was used in the following dehydration step without further purification.

A mixture of 52 g of the crude 1-hydroxy-1-(3,4-methylenedioxyphenyl)pentane and 2 g powdered KHSO4 was heated with a flame until there was no more apparent generation of H2O. The resulting dark, fluid oil was distilled at 100-110 deg C at 0.3 mm/Hg to give 29.5 g of 1-(3,4-methylenedioxyphenyl)-1-pentene as a light yellow liquid. This was employed in the following oxidation step without further purification.

To 120 mL of 90% formic acid there was added, with good stirring, 15 mL H2O, followed by 23 mL of 35% H2O2 To this mixture, cooled with an external ice bath, there was added a solution of 24 g crude 1-(3,4-methylenedioxyphenyl)-1-pentene in 120 mL acetone at a rate slow enough to keep the internal temperature from exceeding 35 deg C. At the end of the addition, the temperature was brought up to 45 deg C by heating briefly on the steam bath, and then the reaction mixture was allowed to stand and stir at ambient temperature for several h. All volatiles were removed under vacuum, with a bath temperature maintained at 45 deg C. The residue was dissolved in 30 mL MeOH, then there was added 200 mL 15% H2SO4 and the mixture held on the steam bath for 1.5 h. There was then added an additional 300 mL H2O, and this was extracted with 2x250 mL of a petroleum ether/EtOAc (5:1) mixture. The extracts were pooled, and the solvents removed under vacuum to give a residue that was distilled at 115-120 deg C at 0.3 mm/Hg. This light yellow liquid weighed 13.5 g and was substantially pure 1-(3,4-methylenedioxyphenyl)-2-pentanone by TLC.

To 5.0 g of aluminum foil cut into 1 inch squares, there was added a solution of 150 mg HgCl2 in 200 mL H2O. The mixture was heated briefly until there were clear signs of active amalgamation, such as fine bubbling for the aluminum surfaces and the beginning of the formation of a gray, amorphous solid phase. The HgCl2 solution was decanted off and the aluminum was washed with 2x200 mL additional H2O. After shaking as dry as possible, there was added, in sequence and with good swirling agitation between each addition, 10 g methylamine hydrochloride in 10 mL H2O, 27 mL IPA, 22 mL of 25% NaOH, 5.0 g 1-(3,4-methylenedioxyphenyl)-2-pentanone, and finally an additional 50 mL IPA. The mixture was heated on the steam bath periodically to maintain the reaction rate at a vigorous boil. When all of the aluminum had been consumed, the cooled mixture was filtered and the solids washed with MeOH. The combined filtrate and washings were stripped of solvent under vacuum. The residue was dissolved in dilute H2SO4 and washed with 2x75 mL CH2Cl2. After making basic again with 25% NaOH, this was extracted with 2x100 mL CH2Cl2, and the pooled extracts were stripped of solvent under vacuum. The residue was distilled at 105-110 deg C at 0.3 mm/Hg to give 2.7 g of a colorless liquid. This was dissolved in 15 mL IPA, neutralized with concentrated HCl, and diluted with 75 mL anhydrous Et2O which allowed a delayed appearance of a fine white crystal. This was removed by filtration, Et2O washed, and air dried to give 2.45 g 2-aminomethyl-1-(3,4-methylenedioxyphenyl)pentane hydrochloride (METHYL-K) as a white product with a mp of 155-156 deg C. Anal. (C13H20ClNO2) C,H.

DOSAGE: greater than 100 mg.

DURATION: unknown.

QUALITATIVE COMMENTS: (with 100 mg) There were no effects. I was busy and totally wound up and didn't sleep until 3 AM, but this was probably unrelated to the Me-K.

EXTENSIONS AND COMMENTARY: The well appears to be running dry, with a pentane chain as a basic skeleton. METHYL-J, at this level, was already showing a number of hints and clues, largely physical such as coldness in the feet and a slight mastoidal pressure, that activity was right around the corner. But METHYL-K gave no such hints. The unmethylated homologue, 2-amino-1-(3,4-methylenedioxyphenyl)pentane (K), was also made, by the reductive amination of 1-(3,4-methylene-dioxyphenyl)-2-pentanone with ammonium acetate and sodium cyanoborohydride in methanol. It was a white crystalline solid, mp 202-203 deg C, but is given here in the comments only, as its human assaying had never even been initiated. Anal. (C12H18ClNO2) C,H. The N-ethyl homologue, 2-ethylamino-1-(3,4-methylene-dioxyphenyl)pentane (ETHYL-K), is entered with its own recipe, on the other hand, since testing had been started with it.

And the longest chain that has been explored in this Muni Metro series is the six-carbon hexyl chain which is, quite logically, the L-series, sort of the end of the Taraval line (see under METHYL-J for an explanation). The central compound for all the L-compounds was the ketone 1-(3,4-methylenedioxyphenyl)-2-hexanone, which was prepared by the Grignard reagent of (n)-amyl bromide with piperonal to give 1-hydroxy-1-(3,4-methylenedioxyphenyl)hexane, dehydration of this with potassium bisulfate to the olefin, and oxidation of this with hydrogen peroxide and formic acid to the L-ketone which was an orange-colored liquid with a bp of 125-135 deg C at 0.3 mm/Hg. This ketone was reductively aminated with ammonium acetate and sodium cyanoborohydride in methanol to produce 2-amino-1-(3,4-methylenedioxyphenyl)hexane hydrochloride (L) as a white crystalline product with a mp of 157-158 deg C. Anal. (C13H20ClNO2) C,H. And this ketone was reductively aminated with methylamine hydrochloride and amalgamated aluminum in isopropanol to produce 2-methylamino-1-(3,4-methylenedioxyphenyl)hexane hydrochloride (METHYL-L) as a white crystalline product with a mp of 139-141 deg C. Anal. (C14H22ClNO2) C,H. The reduction of this ketone in a similar manner with ethylamine hydrochloride produced 2-ethylamino-1-(3,4-methylenedioxyphenyl)hexane (ETHYL-L). None of this series has yet been explored either as psychedelic or entactogenic materials.