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Solvent
Asubstance,usuallyaliquid,thatdissolvessomethingelse
Solute
Asubstancethatisbeingdissolvedinsomethingelse
Solubility
Howeasilyasubstancedissolvesinacertainsolvent
Acid
Asubstancethatgivesupaprotoneasily
Base
Asubstancethatacceptsaprotoneasily
Salt
Theproductfromthereactionofanacidandabase
Freebase
Thenaturalformofadrug,hasn'tbeenreactedwithanacid.
Youcanchangeitbackandforthbetweenitsfreebaseandsaltformasmanytimesasyouwant.

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Mostdrugshaveanaminegroup.ThisisaNH2attachedtothemoleculesomewhere.NH3isabase(acceptsprotons
fromacidseasily)sothedrugsarebasesalso.Hencethenamefreebase.Whenyoumakethedrug,itusuallystarts
outinthefreebaseform,whichisquiteoftenanoil.Whathappenswhenyoureactanacidandabase?Yougetasalt.
Sowhenyoutakeyourfreebase(base)drugandreactitwithanacid,yougetasalt,suchasahydrochloridesaltif
youreactitwithhydrogenchloride(HCl).
Salts are usually crystalline solids rather than oils or waxy solids, which is why they are so popular with drugs, it
makesthemeasiertohandle,andthedrugpropertiesarenotchanged.Thinkaboutit,youhaveHClinyourstomach,
andacidthroughoutyourbody,soifyouingestadrugineitherform,itwillendupbeinginthesameform(probablya
salt)inyourbodynomatterhowitstartedout.
Freebasesandsaltsusuallyhavedrasticallydifferentproperties.Animportantoneisthatfreebasesareusuallysoluble
(will dissolve in) in nonpolar solvents such as toluene and hot naphtha, and not soluble in polar solvents such as
water.Thesaltsareusuallytheopposite,solubleinwater,butnottolueneetc.Thisishowacid/baseextractions(A/B)
work.
YoucanbasifyyourmoleculewithNaOH(lye)toformthefreebase,whichisnotsolubleinwater,butitwilldissolvein
anonpolarsolvent.Soyouaddyournonpolarsolventandthefreebasegoesintoit(alotfasterifyoushakeitallup
insteadofwaitingforthefreebasetofloatuptoit).Onceyouhavefreebaseinyournonpolaryoucanwashthenon
polarsolventwithwatertogetridofanynonfreebasedrugmaterial(suchasexcesslye).Thewaterwillnotremove
anyofyourfreebase.
Then to recover your hydrochloride salt (the most popular form of most drugs), you react it with hydrochloric acid.
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Muriaticacidishydrogenchloride(HCl)dissolvedinwater.Soifyouaddthistothenonpolarwiththefreebase,the
freebasewillreactwiththeHCltoformthesalt,whichisnowsolubleinwaterandnotinnonpolar,soitwilldissolve
intothewaterlayer,whichyoucanseparateandevaporatetoobtainyourcrystals.
Sinceevaporatingwatersucks,andquiteoftenleavesbehindimpurities,itisnicetoreactyourfreebaseinnonpolar
withHClwithoutanywateraround.Thisiswhengassingcomesintoplay.YoucangeneratepureHClwhichisagas
withoutanywater,andbubblethisgasthroughyourfreebase/nonpolar.Itwillreactwithyourfreebasetoformthe
hydrochloridesalt(whatyouwant).Sincethesaltisnotsolubleinthenonpolar,itwillthemfalloutofsolutionas
crystalswhichcanbecollectedbyfiltering.

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Once you have your dry drug hydrochloride salt crystals, sometimes you want to get them more pure, because
impuritiescanbetrappedinsidethetinyclumpsofcrystals.Agoodwayofdoingthisistorecrystallize.Theideabehind
thisistofindasolventthatthecrystalsarekindofsolubleinandkindofnot.Alcoholsusuallyworkwellforthis.When
talkingaboutsolventsandsolidmaterials,hotsolventdissolvesmoresolidthancoldsolvent,sothiscanbeusedto
youradvantage.(ThecaseisoppositeforgasesbutIwon'tgointothat).
Gettwocontainers.Putsomealcoholinoneandbringituptoboiling.Putyourcrystalsintheothercontainer.Slowly
addboilingalcoholtoyourcrystalsandtheywilldissolve.Usejustenoughalcoholtodissolveallofyourcrystals.
Now since cold alcohol doesn't dissolve crystals very well, cool down the
alcohol/product and the crystals will come back out (recrystallize). The slower
youcoolthealcohol,thebiggerthecrystalsare.Thebiggerthecrystalsare,the
fewerimpuritieswillbetrappedinsideofthem,andthepureryourproductwill
be.Sobigcrystals=purecrystals(usually).
Onegoodwayforensuringthatyouralcoholcoolsdownniceandslowistoput
somewaterinapotandheatittoboilingandtakeitoffoftheheat.Thenput
yourcontainerwithhotalcohol/dissolvedcrystalsinthepotofwaterbeingsure
nottogetanywaterintothealcohol,coverthecontainer,andletitcooldown
to room temperature. Then you can put the container with alcohol in the
refridgeratortocoolmore.Thenintothefreezertocoolmore.Thenyoucanfilteryourprettycrystalsout.Nowthere
isusuallystillalittlebitofproductleftinthealcohol,soifyouboiloffsay75%ofthealcoholandrepeatthecooling
processyoucangetsomemorecrystals.
Thereareotherwaysofchangingthesolubilityofthecrystalsinthealcohol,suchasaddingacetoneorethertothe
alcohol, but the temperature method works quite well, is cheap, and simple. So newbies should use it first, then
experimentwithothermethodsiftheywantto.

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Acid/BaseExtractionTutorial(UniversityofAlberta)
ProfessorForkey'sLiquidLiquidExtractionTutorial
ProperRecrystallizationTechnique

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