|PCP ---> meta-nitro-PCP ---> meta-amino-PCP||Bookmark|
This is done in similar fashion fashion as:
Post 391588 (pHarmacist: "4-nitroamphetamine/4-nitromethamphetami
Synthesis of meta-Nitrophencyclidine
To an ice cooled solution of phencyclidine hydrochloride (5 g, 1.8.times.10@-2 mol) in concentrated sulfuric acid (9 ml) was added dropwise, and with stirring, fuming nitric acid (2 ml). The reaction mixture was stirred in an ice-water bath for 1 hour and then poured onto crushed ice/water. The mixture was made basic with 10N sodium hydroxide (50 ml) to pH 12 and extracted with diethyl ether (2.times.100 ml). The combined organic layers were washed with water (2.times.100 ml), dried over anhydrous magnesium sulfate, filtered and evaporated under vacuum. The residue was treated with methyl alcohol (20 ml) and heated on a hot water bath (80 DEG C.) until solute dissolved. The flask was covered with aluminum foil (product is light sensitive) and the solution was allowed to stir at room temperature overnight when a yellow solid precipitated. The solid was collected by filtration and dried under vacuum to afford 3.0 g (58%) of m-nitrophencyclidine as fine yellow crystals which were protected from light: mp 81 DEG -82 DEG C.
Synthesis of meta-Aminophencyclidine
To a stirring solution of m-nitrophencyclidine (3.0 g, 10.4.times.10@-3 mol) in methyl alcohol (150 ml) was added, under a flow of argon, 10% palladium-carbon (0.5 g) followed by ammonium formate (4.0 g, 6.3.times.10@-2 mol). The reaction mixture was stirred at room temperature for 2 hours after which time the catalyst was removed by filtration and the solvent was evaporated under vacuum. The residue was treated with 1N potassium hydroxide solution (30 ml) and extracted with diethyl ether (2.times.50 ml). The combined organic extracts were washed with water (50 ml), dried over anhydrous magnesium sulfate, filtered and evaporated under vacuum. The residue was dissolved in hexane (20 ml) and the solution was stirred at room temperature overnight when a white solid precipitated. The solid was collected by filtration and dried under vacuum to afford 1.4 g (52%) of m-aminophencyclidine: mp 121 DEG-122 DEG C.
Reference: Patent US5331109
Dedicated to: Bwiti
Scroll down to: 1. Substituents at the 3-postition of the phenyl ring at the above link.
But what is also interesting is the introduction of amino group that can readily be replaced by other functional groups thus giving rise to other designer drugs based on PCP. :)
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|Just for fun!||Bookmark|
Speaking about PCP-like compounds, here is new process for preparing norbenzomorphan -the central intermediate- in the preparation of pharmaceutically useful benzomorphan derivatives. Note that this is chemically compleately unrelated to PCP.
1st Reaction step
Ethyl 3-amino-4(3-methoxyphenyl) -2-dimethylbutanoate (4) [R2 =m-CH3 O]
229.3 g (3.5 mol) of zinc in 3.0 liters of dichloromethane are mixed with 230 ml of trimethylchlorosilane under nitrogen and stirred for 20 minutes at ambient temperature. Then 1.1 liters of absolute tetrahydrofuran are added and the mixture is heated to reflux temperature. To this mixture is added dropwise a mixture of 500 g (2.6 mol) of ethyl bromoisobutyrate (1) and 226.4 g (1.5 mol) of m-methoxybenzylcyanide (2) and the resulting mixture is then refluxed for 1.5 hours. It is allowed to cool, decanted off from the excess zinc and after cooling to about 10 DEG C. mixed with 96.7 g (1.5 mol) of sodium cyanoborohydride. Then 300 ml of ethanol are slowly added dropwise (gas evolved). The reaction is allowed to continue for 20 minutes, 1.0 liters of conc. ammonia solution are added, the phases are separated and the organic phase is washed once more with a mixture of 500 ml of conc. ammonia solution and 500 ml of water. The organic phase is dried over sodium sulphate and evaporated down in vacuo. The residue is taken up in 2.3 liters of toluene and extracted twice with 1.8 liters of 2 N hydrochloric acid. Then the aqueous phase is made alkaline with 700 ml of conc. ammonia solution and extracted twice with 2.2 liters of dichloromethane. After the organic phase has been dried over sodium sulphate it is evaporated down in vacuo. The ethyl 3-amino-4-(3-methoxyphenyl) -2-dimethyl-butanoate (4) is isolated in a yield of 322.5 g (81% of theory) as a yellow oil.
2nd Reaction step
382.2 g (1.4 mol) of ethyl 3-amino-4-(3-methoxyphenyl)-2-dimethylbu
3rd Reaction step
469.2 g (1.3 mol) of ethyl 3-(2-ethoxycarbonylethyl)-amino-4-(3-met
4th Reaction step
390.1 g (1.22 mol) of 5-carboethoxy-3,3-dimethyl-2-(3-methoxyp
5th Reaction step
Enantiomer separation of the piperidone (+)-2-(3-Methoxyphenyl)methyl-3,3-dimeth
28.7 g (101 mmol) of 2-(3-methoxyphenyl)methyl-3,3-dimethyl-4
6th Reaction step
24.0 g (60.3 mmol) of (+)-2-(3-methoxyphenyl)methyl-3,3-dimeth
25.7 g (720 mmol) of methyltriphenylphosphonium bromide are suspended in 205 ml of absolute tetrahydrofuran and combined under nitrogen with 8.1 g (720 mmol) of potassium tert.-butoxide at ambient temperature. The mixture is stirred for 30 minutes at 40 DEG C., cooled down to ambient temperature once more and within 10 minutes combined with the above prepared solution of the piperidone in 30 ml of tetrahydrofuran. The resulting mixture is left to react for 1 hour at ambient temperature, cooled to 10 DEG C. and then mixed with 66 ml of water within 15 minutes. The tetrahydrofuran is then eliminated in vacuo and the residue is mixed with 46 ml of dichloromethane and 30 ml of ice water. The phases are separated, the aqueous phase is extracted twice more with 15 ml of dichloromethane and the combined organic extracts are extracted once more with 40 ml of water. Then the mixture is dried over magnesium sulphate, the solvent is eliminated in vacuo, the residue is dissolved in 85 ml of isopropanol and 5.7 ml of conc. hydrochloric acid are added whilst cooling with ice. After 1 hour the mixture is suction filtered (8.5 g), the mother liquor is mixed with 150 ml of diethylether for recrystallisation and after 1 hour it is suction filtered again (5.2 g). The mother liquor is evaporated down in vacuo, the residue is taken up in 30 ml of isopropanol once more and mixed with 200 ml of diethylether. After 3 hours' crystallisation at ambient temperature it is suction filtered (2.1 g) and subsequently all the crystallisation fractions are dried at 60 DEG C. All three fractions proved to be identical according to thin layer chromatography (dichloromethane:methanol:conc. ammonia=95:5:0.1).
In this way the (+)-2-(3-methoxyphenyl)-methyl-3,3-dimet
7th Reaction step
12.7 g (45 mmol) of (+)-2-(3-methoxyphenyl)methyl-3,3-dimeth
8th Reaction step
16 g (120 mmol) of aluminium chloride are placed in 140 ml of dichloromethane at a temperature of -10 DEG C. and 10.9 g (40 mmol) of (+)-N-formyl-2-(3-methoxyphenyl)-methyl-
In this way the (-)-2-formyl-3--methoxy-5,9,9-trimethyl-
9th Reaction step
9.57 g (35 mmol) of (-)-2-formyl-3'-methoxy-5,9,9-trimethyl-
10th Reaction step
10 g (41 mmol) of (-)-3'-methoxy-5,9,9-trimethyl-6,7-benzo
Ref: Patent US5945535
...The best known compound with appreciable affinity for the sigma receptor is the benzomorphan Pentazocine (Talwin, figure 2). This drug is a mixed agonist/antagonist at opiate receptors and generally has lower abuse potential in opiate (ab)users than pure agonists such as morphine. However, this drug is more desired than other opiates by certain users. When it is injected intravenously, especially in combination with an antihistamine (so-called "T's and Blues"), it may produce a euphoric rush that is said to be unique and overwhelmingly pleasurable...
It looks like this family has abuse potential :)
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|Nice contribution! Continue to be naughty!||Bookmark|
Nice contribution! Continue to be naughty! With all the potential hydroxyl-PCA's and other analogs, it's AMAZING that PCP-analogues aren't competing with the sale of nasty-ass, impure, sloppy, black tar heroin and other pain-killers like oxys that contain so many fillers which jam-up your syringe before you get a chance to slam the fucking muck! Thanks for the dedication! Btw, at some point, a hopelessly addicted bear in my dreams will be cooking-up a legal? analogue, using a mixture of diethylamine/benzylamine and posting the synth. Peace!
Love my country, fear my government.