High Bees!
The time has come to provide you with another chapter of the Phenylcyclidine derivate synthesis adventure
Todays target object: TCP
Molecule:
TCP (" C1CCCN(C1)C2(CCCCC2)c3sccc3 ")
Step 1: 2-Thiophene-magnesium bromideTo a 250ml RBF were added 5g (~0,2 mol) of Mg, a crystal of iodine and 50 ml of Et
2O. The apparatus was protected from moisture, and 19,1 ml (0,2 mol) of 2-Bromothiophene in 20ml Et
2O were added dropwise with stirring until the grignard reaction startet. The Bromothiophene was added dropwise during one hour, and after finished addition the mixture was heated to reflux temperature for further 3 hours.
Here are a few pictures how it looks like when a grignard reaction starts:
The ether is coloured by the iodine. The first drops of bromothiophene have been added.
t+ 20 sec. The colour of the iodine disappears, and the ether gets cloudy.
t+ 35 sec. The mixture starts to boil.
t+ 45 sec. Reaction at full blast. grignards are very exothermic. Apply a cold water bath if the reflux becomes to violent!
There´s a lot of info about grignard rnx here at the hive, so UTFSE for details!
Step 2: Salting on the Enamine with anhydrous p-Toluene sulfonic acid32g (0,194 mol) of 1-cyclohexenyl-piperidine (for the preperation of the enamine see
Post 451447
(Xicori: "PCP via enamine intermediate [pictures]", Methods Discourse)) in 80ml of Ether was cooled in an ice bath and dropwise treated with an equimolar amount of anhydrous p-Toluene sulfonic acid in 80ml of Toluene.
Step 3: TCPTo the well stirred & cooled slurry formed in Step 2 was added the grignard solution (Step 1) dropwise. After everything has been added the ice bath was removed and the mixture was stirred for additional 45 minutes.
The grignard solution is added dropwise to the slurry from step 2. Note that all moisture must be excluded!
The mixture after finished addition.
The reaction mixture was poured onto 200ml of crushed ice, and 50g of NH
4Cl and 40ml of concentrated aq. ammonia was added. after some minutes of stirring every solid dissolved and the phases were seperated. The aqueous layer was extracted once more with 100ml of Ether, and then discarded. The combined organic phases were washed twice with 100ml of water and dried over sodium sulfate.
The 2 phases in the sep funnel.
Flask: Combined organic extracts with sodium sulfate added. Beaker: aqueous phase - it can be discarded.
The solvent was removed on the rotary evaporator (Ether at 760mm Hg, Toluene at aspirator vakuum ->solvents can be dried and reused!), and the residue was distilled at 1,5mm Hg.
The residue after removal of the solvents.
High vacuum distillation setup
Freebase in the receiver.
The first fraction consisted of a few drops unreacted 2-Bromothiophene, and the second fraction (TCP freebase) which was collected between 120-140°C @ 1,5mmHg weighted 24,2g.
The freebase oil was dissolved in 40ml of IPA and 8ml of concentrated HCl was added dropwise what was very exothermic. Then 300ml of anhydrous ether was added.
The beaker was placed in the freezer for 30min and was the filtered to yield 22g (~40%, based on the amount of enamine used) of white TCP Hydrochloride.
Product drying in a crystallisation dish.
Bioassay: At SWIMs first try the substance gave him a very good impression. It seems to be more potent than PCP, and also the duration seems to be longer. The main effects are basically the same then with PCP, but the TCP seems to be a bit more colorful
That was SWIMs first experience with TCP, so he hopes that he will be able to give more bioassay information during the next weeks!
Enjoy, and bee safe!
Xicori