High bees!
swim has no chance to get his hands on piperidine and pyrrolidine... and the reduction of pyridine is a bit tricky...
so he wants to try the morpholine analoge of PCP - as far is i know its 1/10 the potency of PCP....still potent enough :)
swim wants to try the route via bisulfite addukt of the cyclohexanone to form the carbonitrile, followed by grignard reaction with phenyl magnesium bromide...
https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/cn_synth.html#pcc2 (https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/cn_synth.html#pcc2)
now some questions:
1.) can the piperidine easily be substituted with morpholine in this reaction without change of the molar ratios?
2.) anybody know: does the carbonitrile crystallise out of solution, or is a extraction with Et2O needed?
3.) Is there any danger of HCN-evolution when quenching the Grignard reaction mixture with aqueous HBr, and does the PCPm-HBr crystallise out of solution?
4.) anybee know if the morpholine-carbonitrile is soluble in ether, or must a ether/hexane mixture be used?
thanks much!
chilito
Post 212050 (https://www.thevespiary.org/talk/index.php?topic=11974.msg21205000#msg21205000)
(hms_beagle: "4-methoxy PCP", Novel Discourse) for example.
you can use the following for tosic acid:
Post 288713 (https://www.thevespiary.org/talk/index.php?topic=9044.msg28871300#msg28871300)
(Chromic: "Getting higher yields with p-tosic acid", Methods Discourse)
Post 261000 (https://www.thevespiary.org/talk/index.php?topic=6776.msg26100000#msg26100000)
(Chromic: "p-toluenesulfonic acid", Chemistry Discourse)
High there again!
swib dissolved his "product" in boiling MeOH, and let it cool down - only very few crystals appeared - so swim decided to add some Et2O to decrease solubility of the HCl-Salt in the mixture - after one night in the freezer swim filtered the whole thing and got ~1g of product (awful yield!!) - FTIR-analysis will be done soon, to see if any nitrile compund is left... i´ll keep you up to date ;)
Now swim wants to give the PCP-M a second chance - he´d like to use a route without any cyanide dangers (i don´t wanna work with KCN again, without an VERY effective fume hood!! - please, dont do it the way i did! :) )
- so there is one method available that looks very nice:
https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/bzp_synth.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/bzp_synth.html)
I think this method could also be applied to N-Benzoylmorpholine...
1. Let Morpholine and Benzoylchloride react under basic conditions, extract with toluene and distill under aspirator vacuum to yield N-Benzoylmorpholine (the procedure can be found @ www.orgsyn org - search fpr "benzoylpiperidine")
2. React the Benzoylmorpholine with 1,5-Dibromopentane as Mg-Grignard to yield PCPm - (https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/bzp_synth.html (https://www.thevespiary.org/rhodium/Rhodium/chemistry/pcp/bzp_synth.html)
)
Now some specific questions concerning step 2:
1. In the article is described to distill off the Et2O until the reaction mixture reaches 83°C. - the mixture is then hold at this temperature for 16 hours.
- why distill off the solvent?
to increase reactivity? would it also work without distilling off the ether and keeping the mixture @ reflux for about 30 hours?
- may there be some danger of peroxide explosion (ether is from unopened bottle, about 6 months old) when distilling ooff the Et2O? - i think tehre shouldnt be to much danger, because there should be some liquid residue in the flask....
- is there any chance to find the boiling point of N-Benzoylmorpholine and the PCPm-freebase - please help here when possible?
-anyone tried this synthesis?
Many thanks!! I´ll make some photos on the synthesis and write an exclusive report :)
many thanks bees,
xicori
hi, xicori. i have no experience at all with cyclidines, but i am
very interested to hear about PCP analogs. i can only give very
general answers.
> why distill off the solvent?
> to increase reactivity? would it also work without distilling
> off the ether and keeping the mixture @ reflux for about 30 hours?
if the text says that 83° is needed for 16h, then it propably is so.
chances are big that the reaction will take an eternety and a half
at 40°.
> - may there be some danger of peroxide explosion (ether is from
> unopened bottle, about 6 months old) when distilling ooff the Et2O?
utfse on ether peroxides. there's everything you need: detection, destruction
and stabilisation.
> - is there any chance to find the boiling point of N-Benzoylmorpholine
> and the PCPm-freebase - please help here when possible?
beilstein crossfire. maybe someone is so kind?
other remarks:
why not use the tosic acid method? tosic acid is very easy to make.
check fallen_angels method: Post 389646 (https://www.thevespiary.org/talk/index.php?topic=9366.msg38964600#msg38964600)
(Antoncho: "Toluenesulfonic acid - tips and tricks.", Methods Discourse).
what worked very well for me was cooking until everything was dissolved,
adding a (calculated) minute amount of H2O (turning the whole mass into a
solid), recrystallising twice from conc HCl and drying over NaOH.
i think PCPm is a misnomer. it should be called PCM or PCMo.
(there's no more piperidine in it!)
have you thought about extracting piperidine from pepper?
that should be easy with an improvised soxhlet (or
even without) and i think many bees would profit from a
working pepper --> piperidine procedure.
________________________
8. If piperidine is available, benzoyl piperidine for use in the preparation of pentamethylene bromide (p. 428) may be prepared by direct benzoylation. A mixture of 105 g. of sodium hydroxide (2.6 moles), 170 g. of piperidine (2.0 moles) (b.p. 104–109°), and 800 cc. of water is treated with 280 g. (2 moles) of benzoyl chloride using the apparatus and procedure described above; the temperature is kept at 35–40°. The oily product is separated after dilution with 250 cc. of benzene if necessary (Note 5), dried with a small quantity of potassium carbonate and distilled. The portion boiling at 172–174° /12 mm. weighs 330–345 g. (87–91 per cent of the theoretical amount). The first few cubic centimeters of the distillate may be colored by a reddish impurity, in which case a forerun is collected separately.
________________________
Cahours, Ann. chim. phys. (3) 38, 87 (1853); Schotten, Ber. 17, 2545 (1884); 21, 2238 (1888).
i think tehre shouldnt be any problems applieing this syntheses to other amines!
Post 391039 (https://www.thevespiary.org/talk/index.php?topic=11308.msg39103900#msg39103900)
(Xicori: "New route to PCP´s?", Novel Discourse) - if this would work, it would be another high yielding, universal synthesis for PCP-Like compounds...
High Bees!
Swim did a FTIR on his samples today... there were two samples:
1.) fine white xtals that seperated out very quickly after cooling from recrystallisation
2.) xtals that crystallized out after a lot of solvent was removed....
The spectra can be seen under
http://members.fortunecity.com/xicori/ (http://members.fortunecity.com/xicori/)
Please look at the spectra... what could substance 1 bee??
Substance 2 is definitevly identified 8)
...there are no peaks for -CN compounds, so swim thinks there shouldnt be any carbonitrile left :)
the substance will be bioassayed today evening 8)
Conclusion:
The synthesis works without doubts, but the yield was very low (bad crystallisation method, a lot was lost during recrystallisation)
best wishes
xicori