Author Topic: beta-Ketophenethylamines (2C-CATs)  (Read 2164 times)

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Rhodium

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beta-Ketophenethylamines (2C-CATs)
« on: March 02, 2004, 03:21:00 PM »
The article below describes a relatively easy method for synthesizing beta-keto-phenethylamines (the two-carbon cathinone analogs). Very few substances of this class has been prepared, and none of them has been evaluated in man as far as I know. As they constitute a middle ground (both sterically and electronically) between the plain phenethylamines (very much active) and the so-called 'BOX series' of beta-methoxy-phenethylamines (active as well), I'd say there is no doubt that these will be active too (as long as the substitution pattern used is one of the highly active 2,5-dimethoxy-4-whatever configurations). The procedure below is exemplified for the 3,4-dimethoxy substituted 2C-CAT analog, but it should be no problem adapting it for the use of 4-bromo-2,5-dimethoxyacetophenone as starting material, for example. Remember that the final aminoketone will dimerize if basified and must stay in salt form at all times (therefore the rather unusual workup in the procedure below).

Synthese des Papaverins
Amé Pictet & Alfons Gams

Chem. Ber. 42, 2943-2952 (1909)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/beta-keto-pea.pdf)

Experimental

Isonitrosoacetoveratrone (CH3O)2C6H3-CO-CH=N-OH
10g 3,4-Dimethoxyacetophenone (Acetoveratrone) was dissolved in a cool sodium ethoxide solution (1.5g Na metal in 30g EtOH), the solution treated with 8g amyl nitrite and allowed to stand in a cool place for 1-2 days. The precipitated sodium salt of isonitrosoacetoveratrone (alpha-oximino-3,4-dimethoxyacetophenone) was filtered off at the pump, washed with cold ether, air dried and recrystallized from ether. The yellow leaflets were dissolved in ice-water and treated with an equimolar amount of glacial acetic acid, which made the free isonitrosoacetoveratrone crystallize in light-yellow needles. After recrystallization from CHCl3 or EtOAc the product had mp 131°C (75% yield).

Amino-acetoveratrone Hydrochloride (CH3O)2C6H3-CO-CH2-NH2·HCl
To 30g anhydrous tin(II)chloride was added 50mL concentrated hydrochloric acid (slowly, with good cooling), and to this solution was added a concentrated solution of 10g isonitrosoacetoveratrone in ethanol, portionwise and with good stirring. After some time, the solution became cloudy and the tin double salt of the product amine crystallized. Concentration of the filtrate gave a second crop of yellowish water-soluble crystals. 10g of this salt was freed from tin by dissolving in 1000ml water and gassing with hydrogen sulfide. After filtering off the tin sulfide precipitate, the solution was evaporated in vacuo to give alpha-amino-acetoveratrone hydrochloride as a yellowish powder, easily soluble in water. After recrystallization from alcohol, the yield of yellow shiny crystals were 6g, mp 185°C (dec.).

The aminoketone free base is unstable and cannot be isolated, upon basification of an aqueous solution of the hydrochloride salt a white precipitate forms, which immediately turns red. The compound has also been synthesized by Friedel-Crafts acylation of veratrole with hippuric acid, see

Patent DE185598

.


The article also describes the synthesis of 3,4-dihydroxyphenylacetic acid from both Eugenol [Ref: Ber. 10, 207 (1877)] and by simultaneous hydrolysis/reduction/demethylation of 3,4-dimethoxymandelonitrile (from veratraldehyde, NaCN and NaHSO3) using 5 eq HI(aq).


Novice

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Rhodium, what beta-hydroxy-phenethylamines are
« Reply #1 on: March 02, 2004, 06:14:00 PM »
Rhodium, what beta-hydroxy-phenethylamines are active, if I might be so bold and ask?

I'm thinking ephedrine, which is merely active in the peripheric nervous system (yet it is probably more lipophilic than most beta-OH-PEA's), and its keto-analog CAT which is slightly more active in the CNS.

What beta-hydroxy-PEA's are you thinking about when stating that beta-OH-PEA's are CNS-active?

Rhodium

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Thanks for pointing out my error
« Reply #2 on: March 02, 2004, 07:00:00 PM »
I'm sorry - I meant to write beta-methoxy-PEAs (I have now corrected the post above), which constitute the 'BOX series' discussed in

Pihkal #14 - BOD

(http://www.erowid.org/library/books_online/pihkal/pihkal014.shtml)

The beta-hydroxy analog of 2C-D has been made, and is called BOHD in Pihkal, but it has not been found active at 50mg.


Nicodem

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ZnCl2?
« Reply #3 on: March 03, 2004, 12:55:00 AM »
I often think about these compounds but wasn't it always considered that the betta-keto-PEA's are way to prone to MAO degradation to have any activity?
Rhodium, do you have anything on these (papers, anecdotal raports...) that the general public still doesn't have?
I read second preparation three times and still don't understand it. Where is the reducent? Could it be that "Zinnechlorur" is SnCl2 and not ZnCl2?


Lilienthal

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"Zinnechlorur" would indeed be ...
« Reply #4 on: March 03, 2004, 01:24:00 AM »
"Zinnechlorur" would indeed be SnCl2.

jsorex

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If 2C-D has these sc.
« Reply #5 on: March 03, 2004, 06:33:00 PM »
If 2C-D has these sc. "smart drug" properties, why doesn't this one? (the beta-methoxy?)


Novice

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Confusion?
« Reply #6 on: March 04, 2004, 06:47:00 AM »
Both 2C-D and its beta-methoxy variant (BOD) are active, as stated above with references to PiHKAL. It's the beta-hydroxy that is inactive...

jsorex

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btw. as a sidenote, ephedrine is not only...
« Reply #7 on: March 04, 2004, 08:10:00 AM »
btw. as a sidenote, ephedrine is not only active in the perpherial nervous system.


dennis_pro

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Activity of substituted ethanolamines
« Reply #8 on: March 05, 2004, 04:22:00 AM »
I personally confirm that 2,5-dimethoxy-4-bromo-phenylethanolamine is active only by parenteral route (i/m) starting from 100 mg. The substance was obtained by hydrolysis and bromination of pharmaceutical "GUTRON (MIDODRINE)"


imp

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A New reduction of Oximes?
« Reply #9 on: March 08, 2004, 10:19:00 PM »
What do you bees think about applying the reduction procedure described to reduce the a-oximino derivative (below), to reducing the oximes described in this paper?...

Post 468014

(imp: "How about these possibilities?", Methods Discourse)


It should be applicable, shouldn't it? GCMS, you might be interested in this? non?



To 30g anhydrous tin(II)chloride was added 50mL concentrated hydrochloric acid (slowly, with good cooling), and to this solution was added a concentrated solution of 10g isonitrosoacetoveratrone in ethanol, portionwise and with good stirring. After some time, the solution became cloudy and the tin double salt of the product amine crystallized. Concentration of the filtrate gave a second crop of yellowish water-soluble crystals. 10g of this salt was freed from tin by dissolving in 1000ml water and gassing with hydrogen sulfide. After filtering off the tin sulfide precipitate, the solution was evaporated in vacuo to give alpha-amino-acetoveratrone hydrochloride as a yellowish powder, easily soluble in water. After recrystallization from alcohol, the yield of yellow shiny crystals were 6g, mp 185°C (dec.).




SnCl2 as the reducing agent from nitroalkene to amine... wow.