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All 26 posts Subject: PCP via enamine intermediate [pictures] Please login to post Down

Xicori
(Hive Bee)
08-03-03 16:20
No 451447
      PCP via enamine intermediate [pictures]
(Rated as: excellent)

High Bees!

After a few trials on PCP-Synthesis via the N-Benzoylpiperidine route (they have all failed, if someone wants details, let me know), Swim has performed a PCP synthesis via the enamine route. The whole synthesis was illustrated with pictures, so that other bees get a easy to follow writeup…

Here we go:

Step 1: N-piperidin-cyclohexene

Into a 250ml RBF with a Dean Stark water-trap, a Dimroth reflux condensor and some boiling stones there were added 39,6ml of Piperidine, 34,5ml of cyclohexanone, 500mg of p-Toluene-sulfonic-acid and 100ml Toluene as solvent.

The mixture was heated with a heating mantle until all water had seperated (~5,4ml). Heating was stopped, and after the contents had cooled down the reaction mixture was washed with ~30ml of water to remove the catalyst acid. The organic phase was seperated, dried over Na2SO4 and distilled under aspirator vacuum to yield 45g of colourless, nearly smellless enamine. (b.p. ~ 108°C@good aspirator vacuum)

Apparatus for azeotropic removal of water

reaction mixture

water in the dean stark receiver

Apparatus for vacuum distillation of the reaction contents

distilled, nearly pure enamine in the recveiver

Note:
Piperidine is corrossive, toxic, and has a very unpleasent amine smell – avoid spilling it -> use a syringe!

Step 2: Removal of water from p-Toluene sulfonic acid Monohydrate

0,1mole (19g) of p-Toluene sulfonic acid Monohydrate were added to 40ml of Toluene, and heated under a Dean stark trap, until no more water seperated, and the distillate was completely clear. Theoretically water amount: 1,8ml

apparatus

boiling mixture

Notes: At first 2 Layers are formed – I think the top layer consists of Toluene, and the bottom layer consists of melted P-Toluene-Sulfonic Acid Monohydrate. -> Use a magnetic stirrer to mix the two phases well. During the seperation of water the bottom layer dissappears -> anhydrous Acid dissolves into the toluene.

Step 3: Preparing of a Phenyl Magnesium Bromide-Solution in Et2O (Grignard-Rnx)

All glassware for this step should be dried in an oven. Anhydrous solvents are absolutely necessary! (use molecular sieves or Na to dry Et2O)

Into a 250ml 3-necked RBF were added 2,4g (01,1 mole) of Mg turnings, 1 small iodine xtal, and 30ml of ether. Now there were slowly added 0,1mole of bromobenzene in 15ml of Et2O. The start of the reaction is noticed by disappearing of the purple iodine-colour, and the ether beginning to boil.
Add the residual Bromobenzene at a rate that keeps the ether refluxing. When all the bromobenzene has been added reflux the mixture for additional 3 hours to finish the reaction.

reaction just started – let bromobenzene drip into the mix slowly

apparatus for grignard rnx – note the drying tubes on condensor and dropping funnel – an effective reflux condensor is also necessary. A liebig-condensor will not work!!

closeup

Notes:

The mixture turns a bit brown during grignard reagent formation. That’s no reason to worry.

When the reaction goes to fast use a cold water bath to slow things down.

Always use magnetic stirring!

Use CaCl2-Drying tubes and an efficient reflux condensor!

Read Organikum, Vogel, etc. about grignard reactions!

Step 4: Salting your enamine from step 1 with your anhydrous acid from step 2

In a 500ml 2-Necked RBF add 16,5g of Cyclohexenyl-Piperidine (from step 1), and add 50ml of anhydrous ether. Add a stirbar, a condensor, a dropping funnel, and attach drying tubes!
Immerse the flask into an ice bath to keep temp below 5°C. Now add your anhydrous P-ToSufoAcid in Toluene, prepared in step 2. – the addition has to be done dropwise.
The enamine forms a salt with the acid (the salt isnt soluble in ether/toluene, so a white slurry is formed).

addition of the anhydrous p-Toluene Sulfonic Acid

a thick white slurry is formed

Note: use a big stirrbar to allow stirring even if the flask contents get a bit sticky.

Step 4: PCP

Now cool your Phenylmagnesium-bromide solution in an ice bath, and transfer the etheral solution into a dropping funnel. All apparatus must be absolutely dry! – Do this as quick as possible to avoid reacting of the Grignard-reagent with humidity/CO2 in the air.

Now add your Grignard-Solution to the slurry produces in Step 4. Cool with ice, and add the solution dropwise! The temp should not go above 5°C. Now the slurry gets easy stirrable again. After everything is added remove the ice bath and stir for additional 30-45min.

Phenyl Magnesium Bromide Solution transferred into dropping funnel.

addition of the grignard reagent.

after finished addition

Now pour the reaction mixture onto 200ml of crushed ice, 20g of NH4Cl and 20ml of concentratet ammonia solution. Let the ice melt and stir well. Everything should go into solution, and 2 layers form.

Transfer the Solution into a seperatory funnel and separate the organic (top) phase.

Extract the water phase once more with 50ml of Ether, and add the extract to the organic phase from above.

Now wash your combined organic phases once with 200ml of water, and dry the organic phase with Na2SO4.

washing with water

freebase in Et2O/Toluene with drying agent added.

After 30min of drying (swirl the flask sometimes) the liquid was decanted and the Na2SO4 was washed with a bit of fresh, dry Et2O. The wash was combined with the etheral solution, and a HCl-Gas generator was set together.

gassing apparatus (gas is dried by a washing bottle filled with CaCl2)

Now the freebase solution is diluted with additional 150ml of anhydrous Et2O, and gassed for ~30sek. Move your gassing tube around to avoid clogging.
when the xtals have settled down gassing is continued until no more crystals appear.

Now the solution was vacuum filtered to leave slight yellow, sticky crystals. The crystals were washed with acetone to leave ~8g of finely white PCP hydrochloride.

Notes: Maybe a acid/base extraction would avoid the stickiness of the xtals.

Be careful with HCl-gas! Its toxic, and highly corrossive!

crystals spring to live

some product drying in an crystallisation dish

Bioassay (~5mg) was used to confirm identity of the substance. – swim had a very dissiociative night, yesterday ;)

So bee safe, have fun!

LG
xicori

flipper
(Hive Bee)
08-04-03 10:30
No 451583
      Great work. Beautiful pic's.

Great work. Beautiful pic's. Thanks.

Aurelius
(Active Asperger Archivist)
08-04-03 19:21
No 451652
      BWITI!!!!

Bwiti absolutely has to see this!   That is a beautiful work! Extra karma on that one!

Hey Rhodium, Please, Please Include this on your site!

(sorry, I got a little excited- PCP is a good thing tongue yummy.)

Act quickly or not at all.

anarae
(Newbee)
08-05-03 03:28
No 451732
      fucking brilliant writeup!

fucking brilliant writeup! nice clean workspace

talk to Rh about putting this on his site?????

raffike
(Hive Addict)
08-05-03 05:51
No 451750
User Picture       Very nice pics,what cam do you use?

Very nice pics,what cam do you use?
Raf has had plans for PCP dream(raf likes DXM,he thinks PCP might be nice too) too but getting precursours(especially piperidine) some seems to be moderately difficult.Glad that posting pics is becoming trend at Hive...

For those about to synth,we salute you

Xicori
(Hive Bee)
08-05-03 07:51
No 451761
      the cam used was a simple digital camera with...

the cam used was a simple digital camera with settings for 640X480 pixels,with some special feature for close-up pictures...

...if you cant get piperidine substitute it with pyrrolidine/morpholine/dimethylamine... especially dimethylamine should produce a very nice compound :)

would be nice to see the writeup on rhodiums page ;)

lg
xicori

Chimimanie
(Hive Bee)
08-05-03 08:21
No 451768
User Picture       Yep, good work

I like it... smile

...and if i was Rhodium i would put it on my page Xicori smile , but hell i am not him. wink

Nice pics BTW. Do you synth in your bathroom or so?

Aurelius
(Active Asperger Archivist)
08-05-03 18:41
No 451853
      Ethoxyethyl analogue

PCEE (ethoxyethyl analog) is very delicious also.

15-30mg is a good start dose. 40mg is wow. and 50-80mg is mind-blowing.

Act quickly or not at all.

Bwiti
(PVC-Analog Taste-Tester)
08-06-03 00:54
No 451948
User Picture       Nice!

I must say that I'm enjoying this thread. cool

Love my country, fear my government.

Rhodium
(Chief Bee)
08-06-03 02:20
No 451976
      Soon...

The pictures are actually hosted from my page, the only thing which is lacking at the moment is a nice HTML doc which links most pictures and shows the 3-4 most interesting ones, along the lines of the docs below:

https://www.rhodium.ws/clandestine/nano/
https://www.rhodium.ws/clandestine/nasa/

Aurelius
(Active Asperger Archivist)
08-06-03 06:14
No 452025
      HTML

I'm working on getting to that stage. I'm not good enough with HTML yet.

Still learning.

Act quickly or not at all.

Xicori
(Hive Bee)
08-06-03 10:13
No 452076
      HTMLizing would be no problem....

HTMLizing would be no problem....

ill send u the document, when finished, rhodium ;)

Barium
(Heavyweight Chempion(eer))
08-06-03 12:22
No 452084
      Wow!

Great post, just great!

The Unworthy

edg3
(Stranger)
08-07-03 18:28
No 452324
      Awesome!

That was a great write up Xicori, brilliant.

"Journey sought in vague dark shadows hidden from lights reflection."

CSIdet
(Stranger)
08-17-03 04:48
No 454044
      Very nice, great equipment

What a pro I have a lot of newbee envey. it's a goal to work toward cool [i][blue]

if at first you don't secced tri tri tri again "DR. WHO "

dioulasso
(Stranger)
08-18-03 13:12
No 454344
      Great!!!

Really cool writeup!

It should work w/ PhMgCl too, right?

Xicori
(Hive Bee)
08-18-03 14:16
No 454354
      yeah, PhMhCl would also work, but bromobenzene

yeah, PhMhCl would also work, but bromobenzene is much more common than chlorobenzene.

goods luck ;)

Bwiti
(PVC-Analog Taste-Tester)
08-20-03 05:13
No 454632
User Picture       Secondary Amines??

"if you cant get piperidine substitute it with pyrrolidine/morpholine/dimethylamine... especially dimethylamine should produce a very nice compound"

In my dreams, I've used diethylamine, and it was a failure. I did the same as you; diethylamine/cyclohexanone --> p-Tosic acid --> Phenyl Grignard. I assumed it was because this method didn't work with diethylamine, but now I'm thinking it was a failure because of my sloppy technique. Am I right? Does the p-tosic method work with all primary and secondary amines? Peace! cool

Love my country, fear my government.

hypo
(Hive Addict)
08-20-03 06:58
No 454657
      hummm...

> Does the p-tosic method work with all primary and secondary amines?

i think the Mg-grignard only works withg secondary amines, who form
an enamine intermediate. primary amines, forming an imine intermediate
might need an Li-grignard. phenyl grignards are pretty weak.

but this is from the top of my head, so take with some rock salt.

n'importe quoi

synthon
(Stranger)
06-12-04 03:11
No 512905
User Picture       On Xicori's old post...

Hi Xicori!

I red one of your earlier posts; it is impossible to reply to it, so I post the reply here, incredibly, there were no replies to it; Post 391039 (Xicori: "New route to PCP´s?", Novel Discourse). You wanted to transform 1-Phenylcyclohexanol to (1-bromocyclohexyl)-benzene. (1-iodocyclohexyl)-benzene would work as well in the synthesis. It could be prepared using the notorious iodine/red phosphorous method. Aluminium and iodine might be adequate for this purpose as well. It works well with the simple alcohols (MeOH, EtOH…), giving generally lower (than rP/I2) but still excellent yields, see: Jones; Green; J.Chem.Soc.; 1926; 2760; J.Chem.Soc.; 1927; 928. Tosylation/mesylation of the 1-Phenylcyclohexanol is maybe yet another option?

Another more OTC and hence interesting approach would be to simply gas the alcohol with HCl in DCM, see: H.; Tsushima,T.; J.Amer.Chem.Soc.; 92; 1970; 3397-3403. and Arumugam,N. et al.; Indian J.Chem.Sect.B; 16; 1978; 917-920 - both describe the synthesis of (1-chloroyclohexyl)-benzene using conc. HCl (or gas?). Finally, there is a paper where they react (I) with various amines, amides...: Baiocchi,L. et al.; Gazz.Chim.Ital.; 103; 1973; 61-69.. Might be worth checking it out for the yields/chemistry as many different nucleophiles were used, unfortunately I can't get it...

Nicodem
(Hive Bee)
06-12-04 09:24
No 512938
User Picture       tertiary halides give elimination products

You can't use nucleophylic substitution on tertiary halides (or pseudohalides) because they give mostly just the elimination product. The classical example thought in the school books is t-butyl-chloride which gives mostly isobutene while tBu-OH is the minor product of the solvolysis. I guess it would bee possible to use very mild conditions to give some PCP but it would always bee the in low yields.

“The real drug-problem is that we need more and better drugs.” – J. Ott

synthon
(Stranger)
06-12-04 14:14
No 512970
User Picture       J. Am. Chem. Soc.; 1988; 110(20); 6818-6825:
(Rated as: good read)

2-Phenyl-2-bromopropane: A solution of 33 g of PBr3 (0.12 mol) in 55 mL of chloroform was added dropwise at 40 C to a stirred solution of 50 g of a,a-dimethylbenzyl alcohol (0.36 mol) in 700 mL of chloroform.The reaction mixture was stirred for 2 h at 40 C. The chloroform layer was separated from the viscous inorganic layer and poured into 500 mL of ice water. The organic layer was separated, washed twice with a saturated aqueous Na₂CO₃ solution and once with water, and dried over MgSO₄. The chloroform was removed under reduced pressure. After distillation a colorless liquid was obtained; boiling region 57-80 C (0.05 mmHg). The product contained 31% of the elimination product a-methylstyrene. The product was used without further purification for the synthesis of lf. The yield of 2-phenyl-2-bromopropane was 57%

a,a-Dimethylbenzylamine: This amine was obtained by treatment of 2-phenyl-2-bromopropane with liquid ammonia.^* After evaporation of the ammonia, the product was dissolved in 1 M aqueous HCl and the a-methylstyrene was extracted with diethyl ether. The water layer was brought to pH 14, and the free amine was extracted with ether. The ether layer was dried over MgSO₄, and the ether removed under reduced pressure. The yield was 53%

*:_{Brander, M. M. Red. Trm. Chim. Puys-Bus Belg. 1918,37,76-87.}

I agree, the yields are not the best..

Alcohols/Alkenes to chlorides:

A Convenient Procedure for the Quantitative Conversion of Reactive Alcohols and Olefins into the Corresponding Chlorides
Herbert C. Brown, Min-Hon Rei;
J. Org. Chem.; 1966; 31(4); 1090-1093.

..and refs in there.

Nicodem
(Hive Bee)
06-12-04 16:05
No 512992
User Picture       That is not a bad yield

Actually a yield of 53% is about two times better than I thought it is smile . That is quite a decent yield. But you have to consider the very low temperature used (-33°C) and the ammonia being a weaker base than piperidine. I guess piperidine in a non-polar solvent like CH2Cl2 that would inhibit carbocation formation and working at <-10°C temperature would still give about a 30% yield. And you could even recycle the 1-phenyl-cyclohexene side product.
The other bad thing is that converting the alcohol to the halide causes the same problem of H2O elimination. However, there are conditions that should give a good yield even when using conc. HCl. One is by adding a PTC catalyst because you would then have the same conditions needed for the benzylic –OH substitution as well as double bond hydrochlorination of any 1-phenyl-cyclohexene that would form from the elimination pathway.

But you still need a phenyl Grignard to prepare 1-phenyl-cyclohexanol so why should this bee any better than preparing PCP directly with the usual method?

( If you find a paper where the preparation of 1-phenyl-cyclohexene is described by the condensation of benzene and cyclohexanone then this method would prove to bee an excellent alternative. )

“The real drug-problem is that we need more and better drugs.” – J. Ott

ning
(acetaminophanatic)
06-12-04 16:25
No 512998
User Picture       Urea?

Can't urea convert directly tertiary alcohols to amines in acidic conditions, by SN1 reaction, followed by hydrolysis? Yields were supposed to be good.

In this case, one would have to alkylate the amine later. I think a reductive amination with actone or methyl ethyl ketone sounds nice and attractive. Perhaps even direct alkylation with alkyl halide would work, due to steric hinderance preventing overalkylation.

Perhaps pyrolysis of PCA with pyran would give PCP directly-- if I remember correctly, one way piperazine is made is by pyrolysis of morpholine with ammonia.

_{Drugs are Gods. Respect them.}

synthon
(Stranger)
06-13-04 17:22
No 513173
User Picture       Oh, what a great idea, Ning...

_{Many thanks to Nicodem on the Ritter-type of reactions and their use for this purpose. At the espacenet a patent was found based on Ning's idea that tert. alcohols can be treated with urea and conc. H2SO4 to give condensation products, which upon hydrolysis give amines.}

PCA intermediate is very interesting as simple reductive amination with various ketones/aldehydes can give a spectrum of extreamly potent analogues.

Tertiary Alkyl Urea and Process for Preparing Same: Patent US2247495

acx01b
(Stranger)
10-11-04 22:39
No 535415
      in the patent, with the urea way they get...

in the patent, with the urea way they get seventy percent of MONO tertiary butyl urea...

but (tert-butyl)-NH-CO-NH-(tert-butyl) can exist too :-)
(why would it not exist??)
so maybe the total yield of pca from pcoh is not far from 90+ %...

	https://the-hive.archive.erowid.org	the-hive@erowid.org



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	All 26 posts		Subject: PCP via enamine intermediate [pictures]		Please login to post		Down


		Xicori (Hive Bee) 08-03-03 16:20 No 451447				PCP via enamine intermediate [pictures] (Rated as: excellent)
						High Bees! After a few trials on PCP-Synthesis via the N-Benzoylpiperidine route (they have all failed, if someone wants details, let me know), Swim has performed a PCP synthesis via the enamine route. The whole synthesis was illustrated with pictures, so that other bees get a easy to follow writeup… Here we go: Step 1: N-piperidin-cyclohexene Into a 250ml RBF with a Dean Stark water-trap, a Dimroth reflux condensor and some boiling stones there were added 39,6ml of Piperidine, 34,5ml of cyclohexanone, 500mg of p-Toluene-sulfonic-acid and 100ml Toluene as solvent. The mixture was heated with a heating mantle until all water had seperated (~5,4ml). Heating was stopped, and after the contents had cooled down the reaction mixture was washed with ~30ml of water to remove the catalyst acid. The organic phase was seperated, dried over Na2SO4 and distilled under aspirator vacuum to yield 45g of colourless, nearly smellless enamine. (b.p. ~ 108°C@good aspirator vacuum) Apparatus for azeotropic removal of water reaction mixture water in the dean stark receiver Apparatus for vacuum distillation of the reaction contents distilled, nearly pure enamine in the recveiver Note: Piperidine is corrossive, toxic, and has a very unpleasent amine smell – avoid spilling it -> use a syringe! Step 2: Removal of water from p-Toluene sulfonic acid Monohydrate 0,1mole (19g) of p-Toluene sulfonic acid Monohydrate were added to 40ml of Toluene, and heated under a Dean stark trap, until no more water seperated, and the distillate was completely clear. Theoretically water amount: 1,8ml apparatus boiling mixture Notes: At first 2 Layers are formed – I think the top layer consists of Toluene, and the bottom layer consists of melted P-Toluene-Sulfonic Acid Monohydrate. -> Use a magnetic stirrer to mix the two phases well. During the seperation of water the bottom layer dissappears -> anhydrous Acid dissolves into the toluene. Step 3: Preparing of a Phenyl Magnesium Bromide-Solution in Et2O (Grignard-Rnx) All glassware for this step should be dried in an oven. Anhydrous solvents are absolutely necessary! (use molecular sieves or Na to dry Et2O) Into a 250ml 3-necked RBF were added 2,4g (01,1 mole) of Mg turnings, 1 small iodine xtal, and 30ml of ether. Now there were slowly added 0,1mole of bromobenzene in 15ml of Et2O. The start of the reaction is noticed by disappearing of the purple iodine-colour, and the ether beginning to boil. Add the residual Bromobenzene at a rate that keeps the ether refluxing. When all the bromobenzene has been added reflux the mixture for additional 3 hours to finish the reaction. reaction just started – let bromobenzene drip into the mix slowly apparatus for grignard rnx – note the drying tubes on condensor and dropping funnel – an effective reflux condensor is also necessary. A liebig-condensor will not work!! closeup Notes: The mixture turns a bit brown during grignard reagent formation. That’s no reason to worry. When the reaction goes to fast use a cold water bath to slow things down. Always use magnetic stirring! Use CaCl2-Drying tubes and an efficient reflux condensor! Read Organikum, Vogel, etc. about grignard reactions! Step 4: Salting your enamine from step 1 with your anhydrous acid from step 2 In a 500ml 2-Necked RBF add 16,5g of Cyclohexenyl-Piperidine (from step 1), and add 50ml of anhydrous ether. Add a stirbar, a condensor, a dropping funnel, and attach drying tubes! Immerse the flask into an ice bath to keep temp below 5°C. Now add your anhydrous P-ToSufoAcid in Toluene, prepared in step 2. – the addition has to be done dropwise. The enamine forms a salt with the acid (the salt isnt soluble in ether/toluene, so a white slurry is formed). addition of the anhydrous p-Toluene Sulfonic Acid a thick white slurry is formed Note: use a big stirrbar to allow stirring even if the flask contents get a bit sticky. Step 4: PCP Now cool your Phenylmagnesium-bromide solution in an ice bath, and transfer the etheral solution into a dropping funnel. All apparatus must be absolutely dry! – Do this as quick as possible to avoid reacting of the Grignard-reagent with humidity/CO2 in the air. Now add your Grignard-Solution to the slurry produces in Step 4. Cool with ice, and add the solution dropwise! The temp should not go above 5°C. Now the slurry gets easy stirrable again. After everything is added remove the ice bath and stir for additional 30-45min. Phenyl Magnesium Bromide Solution transferred into dropping funnel. addition of the grignard reagent. after finished addition Now pour the reaction mixture onto 200ml of crushed ice, 20g of NH4Cl and 20ml of concentratet ammonia solution. Let the ice melt and stir well. Everything should go into solution, and 2 layers form. Transfer the Solution into a seperatory funnel and separate the organic (top) phase. Extract the water phase once more with 50ml of Ether, and add the extract to the organic phase from above. Now wash your combined organic phases once with 200ml of water, and dry the organic phase with Na2SO4. washing with water freebase in Et2O/Toluene with drying agent added. After 30min of drying (swirl the flask sometimes) the liquid was decanted and the Na2SO4 was washed with a bit of fresh, dry Et2O. The wash was combined with the etheral solution, and a HCl-Gas generator was set together. gassing apparatus (gas is dried by a washing bottle filled with CaCl2) Now the freebase solution is diluted with additional 150ml of anhydrous Et2O, and gassed for ~30sek. Move your gassing tube around to avoid clogging. when the xtals have settled down gassing is continued until no more crystals appear. Now the solution was vacuum filtered to leave slight yellow, sticky crystals. The crystals were washed with acetone to leave ~8g of finely white PCP hydrochloride. Notes: Maybe a acid/base extraction would avoid the stickiness of the xtals. Be careful with HCl-gas! Its toxic, and highly corrossive! crystals spring to live some product drying in an crystallisation dish Bioassay (~5mg) was used to confirm identity of the substance. – swim had a very dissiociative night, yesterday ;) So bee safe, have fun! LG xicori



		flipper (Hive Bee) 08-04-03 10:30 No 451583				Great work. Beautiful pic's.
						Great work. Beautiful pic's. Thanks.



		Aurelius (Active Asperger Archivist) 08-04-03 19:21 No 451652				BWITI!!!!
						Bwiti absolutely has to see this! That is a beautiful work! Extra karma on that one! Hey Rhodium, Please, Please Include this on your site! (sorry, I got a little excited- PCP is a good thing yummy.) Act quickly or not at all.



		anarae (Newbee) 08-05-03 03:28 No 451732				fucking brilliant writeup!
						fucking brilliant writeup! nice clean workspace talk to Rh about putting this on his site?????



		raffike (Hive Addict) 08-05-03 05:51 No 451750				Very nice pics,what cam do you use?
						Very nice pics,what cam do you use? Raf has had plans for PCP dream(raf likes DXM,he thinks PCP might be nice too) too but getting precursours(especially piperidine) some seems to be moderately difficult.Glad that posting pics is becoming trend at Hive... For those about to synth,we salute you



		Xicori (Hive Bee) 08-05-03 07:51 No 451761				the cam used was a simple digital camera with...
						the cam used was a simple digital camera with settings for 640X480 pixels,with some special feature for close-up pictures... ...if you cant get piperidine substitute it with pyrrolidine/morpholine/dimethylamine... especially dimethylamine should produce a very nice compound :) would be nice to see the writeup on rhodiums page ;) lg xicori



		Chimimanie (Hive Bee) 08-05-03 08:21 No 451768				Yep, good work
						I like it... ...and if i was Rhodium i would put it on my page Xicori, but hell i am not him. Nice pics BTW. Do you synth in your bathroom or so?



		Aurelius (Active Asperger Archivist) 08-05-03 18:41 No 451853				Ethoxyethyl analogue
						PCEE (ethoxyethyl analog) is very delicious also. 15-30mg is a good start dose. 40mg is wow. and 50-80mg is mind-blowing. Act quickly or not at all.



		Bwiti (PVC-Analog Taste-Tester) 08-06-03 00:54 No 451948				Nice!
						I must say that I'm enjoying this thread. Love my country, fear my government.



		Rhodium (Chief Bee) 08-06-03 02:20 No 451976				Soon...
						The pictures are actually hosted from my page, the only thing which is lacking at the moment is a nice HTML doc which links most pictures and shows the 3-4 most interesting ones, along the lines of the docs below: https://www.rhodium.ws/clandestine/nano/ https://www.rhodium.ws/clandestine/nasa/



		Aurelius (Active Asperger Archivist) 08-06-03 06:14 No 452025				HTML
						I'm working on getting to that stage. I'm not good enough with HTML yet. Still learning. Act quickly or not at all.



		Xicori (Hive Bee) 08-06-03 10:13 No 452076				HTMLizing would be no problem....
						HTMLizing would be no problem.... ill send u the document, when finished, rhodium ;)



		Barium (Heavyweight Chempion(eer)) 08-06-03 12:22 No 452084				Wow!
						Great post, just great! The Unworthy



		edg3 (Stranger) 08-07-03 18:28 No 452324				Awesome!
						That was a great write up Xicori, brilliant. "Journey sought in vague dark shadows hidden from lights reflection."



		CSIdet (Stranger) 08-17-03 04:48 No 454044				Very nice, great equipment
						What a pro I have a lot of newbee envey. it's a goal to work toward[i][blue] if at first you don't secced tri tri tri again "DR. WHO "



		dioulasso (Stranger) 08-18-03 13:12 No 454344				Great!!!
						Really writeup! It should work w/ PhMgCl too, right?



		Xicori (Hive Bee) 08-18-03 14:16 No 454354				yeah, PhMhCl would also work, but bromobenzene
						yeah, PhMhCl would also work, but bromobenzene is much more common than chlorobenzene. goods luck ;)



		Bwiti (PVC-Analog Taste-Tester) 08-20-03 05:13 No 454632				Secondary Amines??
						"if you cant get piperidine substitute it with pyrrolidine/morpholine/dimethylamine... especially dimethylamine should produce a very nice compound" In my dreams, I've used diethylamine, and it was a failure. I did the same as you; diethylamine/cyclohexanone --> p-Tosic acid --> Phenyl Grignard. I assumed it was because this method didn't work with diethylamine, but now I'm thinking it was a failure because of my sloppy technique. Am I right? Does the p-tosic method work with all primary and secondary amines? Peace! Love my country, fear my government.



		hypo (Hive Addict) 08-20-03 06:58 No 454657				hummm...
						> Does the p-tosic method work with all primary and secondary amines? i think the Mg-grignard only works withg secondary amines, who form an enamine intermediate. primary amines, forming an imine intermediate might need an Li-grignard. phenyl grignards are pretty weak. but this is from the top of my head, so take with some rock salt. n'importe quoi



		synthon (Stranger) 06-12-04 03:11 No 512905				On Xicori's old post...
						Hi Xicori! I red one of your earlier posts; it is impossible to reply to it, so I post the reply here, incredibly, there were no replies to it; Post 391039 (Xicori: "New route to PCP´s?", Novel Discourse). You wanted to transform 1-Phenylcyclohexanol to (1-bromocyclohexyl)-benzene. (1-iodocyclohexyl)-benzene would work as well in the synthesis. It could be prepared using the notorious iodine/red phosphorous method. Aluminium and iodine might be adequate for this purpose as well. It works well with the simple alcohols (MeOH, EtOH…), giving generally lower (than rP/I2) but still excellent yields, see: Jones; Green; J.Chem.Soc.; 1926; 2760; J.Chem.Soc.; 1927; 928. Tosylation/mesylation of the 1-Phenylcyclohexanol is maybe yet another option? Another more OTC and hence interesting approach would be to simply gas the alcohol with HCl in DCM, see: H.; Tsushima,T.; J.Amer.Chem.Soc.; 92; 1970; 3397-3403. and Arumugam,N. et al.; Indian J.Chem.Sect.B; 16; 1978; 917-920 - both describe the synthesis of (1-chloroyclohexyl)-benzene using conc. HCl (or gas?). Finally, there is a paper where they react (I) with various amines, amides...: Baiocchi,L. et al.; Gazz.Chim.Ital.; 103; 1973; 61-69.. Might be worth checking it out for the yields/chemistry as many different nucleophiles were used, unfortunately I can't get it...



		Nicodem (Hive Bee) 06-12-04 09:24 No 512938				tertiary halides give elimination products
						You can't use nucleophylic substitution on tertiary halides (or pseudohalides) because they give mostly just the elimination product. The classical example thought in the school books is t-butyl-chloride which gives mostly isobutene while tBu-OH is the minor product of the solvolysis. I guess it would bee possible to use very mild conditions to give some PCP but it would always bee the in low yields. “The real drug-problem is that we need more and better drugs.” – J. Ott



		synthon (Stranger) 06-12-04 14:14 No 512970				J. Am. Chem. Soc.; 1988; 110(20); 6818-6825: (Rated as: good read)
						2-Phenyl-2-bromopropane: A solution of 33 g of PBr3 (0.12 mol) in 55 mL of chloroform was added dropwise at 40 C to a stirred solution of 50 g of a,a-dimethylbenzyl alcohol (0.36 mol) in 700 mL of chloroform.The reaction mixture was stirred for 2 h at 40 C. The chloroform layer was separated from the viscous inorganic layer and poured into 500 mL of ice water. The organic layer was separated, washed twice with a saturated aqueous Na₂CO₃ solution and once with water, and dried over MgSO₄. The chloroform was removed under reduced pressure. After distillation a colorless liquid was obtained; boiling region 57-80 C (0.05 mmHg). The product contained 31% of the elimination product a-methylstyrene. The product was used without further purification for the synthesis of lf. The yield of 2-phenyl-2-bromopropane was 57% a,a-Dimethylbenzylamine: This amine was obtained by treatment of 2-phenyl-2-bromopropane with liquid ammonia.^* After evaporation of the ammonia, the product was dissolved in 1 M aqueous HCl and the a-methylstyrene was extracted with diethyl ether. The water layer was brought to pH 14, and the free amine was extracted with ether. The ether layer was dried over MgSO₄, and the ether removed under reduced pressure. The yield was 53% :_{Brander, M. M. Red. Trm. Chim. Puys-Bus Belg. 1918,37,76-87.} I agree, the yields are not the best.. Alcohols/Alkenes to chlorides: A Convenient Procedure for the Quantitative Conversion of Reactive Alcohols and Olefins into the Corresponding Chlorides* Herbert C. Brown, Min-Hon Rei; J. Org. Chem.; 1966; 31(4); 1090-1093. ..and refs in there.



		Nicodem (Hive Bee) 06-12-04 16:05 No 512992				That is not a bad yield
						Actually a yield of 53% is about two times better than I thought it is. That is quite a decent yield. But you have to consider the very low temperature used (-33°C) and the ammonia being a weaker base than piperidine. I guess piperidine in a non-polar solvent like CH2Cl2 that would inhibit carbocation formation and working at <-10°C temperature would still give about a 30% yield. And you could even recycle the 1-phenyl-cyclohexene side product. The other bad thing is that converting the alcohol to the halide causes the same problem of H2O elimination. However, there are conditions that should give a good yield even when using conc. HCl. One is by adding a PTC catalyst because you would then have the same conditions needed for the benzylic –OH substitution as well as double bond hydrochlorination of any 1-phenyl-cyclohexene that would form from the elimination pathway. But you still need a phenyl Grignard to prepare 1-phenyl-cyclohexanol so why should this bee any better than preparing PCP directly with the usual method? ( If you find a paper where the preparation of 1-phenyl-cyclohexene is described by the condensation of benzene and cyclohexanone then this method would prove to bee an excellent alternative. ) “The real drug-problem is that we need more and better drugs.” – J. Ott



		ning (acetaminophanatic) 06-12-04 16:25 No 512998				Urea?
						Can't urea convert directly tertiary alcohols to amines in acidic conditions, by SN1 reaction, followed by hydrolysis? Yields were supposed to be good. In this case, one would have to alkylate the amine later. I think a reductive amination with actone or methyl ethyl ketone sounds nice and attractive. Perhaps even direct alkylation with alkyl halide would work, due to steric hinderance preventing overalkylation. Perhaps pyrolysis of PCA with pyran would give PCP directly-- if I remember correctly, one way piperazine is made is by pyrolysis of morpholine with ammonia. _{Drugs are Gods. Respect them.}



		synthon (Stranger) 06-13-04 17:22 No 513173				Oh, what a great idea, Ning...
						_{Many thanks to Nicodem on the Ritter-type of reactions and their use for this purpose. At the espacenet a patent was found based on Ning's idea that tert. alcohols can be treated with urea and conc. H2SO4 to give condensation products, which upon hydrolysis give amines.} PCA intermediate is very interesting as simple reductive amination with various ketones/aldehydes can give a spectrum of extreamly potent analogues. Tertiary Alkyl Urea and Process for Preparing Same: Patent US2247495



		acx01b (Stranger) 10-11-04 22:39 No 535415				in the patent, with the urea way they get...
						in the patent, with the urea way they get seventy percent of MONO tertiary butyl urea... but (tert-butyl)-NH-CO-NH-(tert-butyl) can exist too :-) (why would it not exist??) so maybe the total yield of pca from pcoh is not far from 90+ %...

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