1-pcp synthesis pictorial

8/9/2019 1-Pcp Synthesis Pictorial

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PCP via Enamine Intermediate

by Xicori

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After a few trials on PCP-Synthesis via the -Ben!oyl"i"eridine ro#te $they

have all failed% if someone wants details% let me know&% Swim has "erformed a

PCP synthesis via the enamine ro#te' (he whole synthesis was ill#strated with

"ict#res% so that other bees )et a easy to follow write#"*

+ere we )o,

Ste" , -"i"eridin-cyclohe.ene

Into a /01ml 2B3 with a 4ean Stark water-tra"% a 4imroth re5#. condensor

and some boilin) stones there were added 67%8ml of Pi"eridine% 69%0ml ofcyclohe.anone% 011m) of "-(ol#ene-s#lfonic-acid and 11ml (ol#ene as

solvent'

(he mi.t#re was heated with a heatin) mantle #ntil all water had se"erated

$:0%9ml&' +eatin) was sto""ed% and after the contents had cooled down the

reaction mi.t#re was washed with :61ml of water to remove the catalyst

acid' (he or)anic "hase was se"erated% dried over a/S;9 and distilled

#nder as"irator vac##m to yield 90) of colo#rless% nearly smellless enamine'

$b'"' : 1)ood as"irator vac##m&


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A""arat#s for a!eotro"ic removal of water

/& 2eaction ?i.t#re


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6& water in the dean stark receiver


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9& A""arat#s for vac##m distillation of the reaction contents


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0& distilled% nearly "#re enamine in the recveiver


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ote,


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Pi"eridine is corrossive% to.ic% and has a very #n"leasent amine smell @ avoid

s"illin) it - #se a syrin)e

Ste" /, 2emoval of water from "-(ol#ene s#lfonic acid ?onohydrate

1%mole $7)& of "-(ol#ene s#lfonic acid ?onohydrate were added to 91ml of

(ol#ene% and heated #nder a 4ean stark tra"% #ntil no more water se"erated%

and the distillate was com"letely clear' (heoretically water amo#nt, %


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& boilin) mi.t#re


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otes, At Drst / ayers are formed @ I think the to" layer consists of (ol#ene%

and the bottom layer consists of melted P-(ol#ene-S#lfonic Acid ?onohydrate'

- Fse a ma)netic stirrer to mi. the two "hases well' 4#rin) the se"eration

of water the bottom layer dissa""ears - anhydro#s Acid dissolves into the

tol#ene'

Ste" 6, Pre"arin) of a Phenyl ?a)nesi#m Bromide-Sol#tion in Et/; $Gri)nard-

2n.&

All )lassware for this ste" sho#ld be dried in an oven' Anhydro#s solvents areabsol#tely necessary $#se molec#lar sieves or a to dry Et/;&

Into a /01ml 6-necked 2B3 were added /%9) $1% mole& of ?) t#rnin)s%

small iodine .tal% and 61ml of ether' ow there were slowly added 1%mole of

bromoben!ene in 0ml of Et/;' (he start of the reaction is noticed by


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disa""earin) of the "#r"le iodine-colo#r% and the ether be)innin) to boil'

Add the resid#al Bromoben!ene at a rate that kee"s the ether re5#.in)'

Hhen all the bromoben!ene has been added re5#. the mi.t#re for additional

6 ho#rs to Dnish the reaction'

reaction #st started @ let bromoben!ene dri" into the mi. slowly


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7& Close#"


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otes,

(he mi.t#re t#rns a bit brown d#rin) )ri)nard rea)ent formation' (hatKs no

reason to worry'

Hhen the reaction )oes to fast #se a cold water bath to slow thin)s down'

Always #se ma)netic stirrin)

Fse CaCl/-4ryin) t#bes and an eLcient re5#. condensor

2ead ;r)anik#m% Mo)el% etc' abo#t )ri)nard reactions


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Ste" 9, Saltin) yo#r enamine from ste" with yo#r anhydro#s acid from ste"

/

In a 011ml /-ecked 2B3 add 8%0) of Cyclohe.enyl-Pi"eridine $from ste" &%

and add 01ml of anhydro#s ether' Add a stirbar% a condensor% a dro""in)

f#nnel% and attach dryin) t#bes

Immerse the 5ask into an ice bath to kee" tem" below 0=C' ow add yo#r

anhydro#s P-(oS#foAcid in (ol#ene% "re"ared in ste" /' @ the addition has to

be done dro"wise'

(he enamine forms a salt with the acid $the salt isnt sol#ble in etherNtol#ene%

so a white sl#rry is formed&'

1& addition of the anhydro#s "-(ol#ene S#lfonic Acid


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& a thick white sl#rry is formed


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ote, #se a bi) stirrbar to allow stirrin) even if the 5ask contents )et a bit

sticky

Ste" 9, PCP

ow cool yo#r Phenylma)nesi#m-bromide sol#tion in an ice bath% and

transfer the etheral sol#tion into a dro""in) f#nnel' All a""arat#s m#st beabsol#tely dry @ 4o this as O#ick as "ossible to avoid reactin) of the

Gri)nard-rea)ent with h#midityNC;/ in the air'

ow add yo#r Gri)nard-Sol#tion to the sl#rry "rod#ced in Ste" 9' Cool with

ice% and add the sol#tion dro"wise (he tem" sho#ld not )o above 0=C' ow


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the sl#rry )ets easy stirrable a)ain' After everythin) is added remove the ice

bath and stir for additional 61-90min'

/& Phenyl ?a)nesi#m Bromide Sol#tion transferred into dro""in) f#nnel'

addition of the )ri)nard rea)ent'

6& 4#rin) Addition


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9& Addition Dnished


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ow "o#r the reaction mi.t#re onto /11ml of cr#shed ice% /1) of +9Cl and

/1ml of concentratet ammonia sol#tion' et the ice melt and stir well'

Everythin) sho#ld )o into sol#tion% and / layers form'

(ransfer the Sol#tion into a se"eratory f#nnel and se"arate the or)anic $to"&

"hase'

0& the / "hases in the se"eratory f#nnel


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E.tract the water "hase once more with 01ml of Ether% and add the e.tract to

the or)anic "hase from above'

ow wash yo#r combined or)anic "hases once with /11ml of water% and dry

the or)anic "hase with a/S;9'


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8& washin) with water

& freebase in Et/;N(ol#ene with dryin) a)ent added'


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After 61min of dryin) $swirl the 5ask sometimes& the liO#id was decanted and

the a/S;9 was washed with a bit of fresh% dry Et/;' (he wash was

combined with the etheral sol#tion% and a +Cl-Gas )enerator was set

to)ether'


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ow the freebase sol#tion is dil#ted with additional 01ml of anhydro#s Et/;%

and )assed for :61sek' ?ove yo#r )assin) t#be aro#nd to avoid clo))in)'

when the .tals have settled down )assin) is contin#ed #ntil no more crystals

a""ear'

ow the sol#tion was vac##m Dltered to leave sli)ht yellow% sticky crystals'

(he crystals were washed with acetone to leave :


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7& crystals s"rin) to live

/1& some "rod#ct dryin) in an crystallisation dish


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Bioassay $:0m)& was #sed to conDrm identity of the s#bstance' @ swim had a

very dissiociative ni)ht &

So bee safe% have f#n

G

.icori

1-pcp synthesis pictorial

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